Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)

Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Goldfarb L.G. [verfasserIn] Platonov F.A. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch ; Russisch

Erschienen:	2020

Schlagwörter:	republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion

Übergeordnetes Werk:	In: Сибирские исследования - Сибирские исследования, 2021, 2(2020), 2, Seite 62-73
Übergeordnetes Werk:	volume:2 ; year:2020 ; number:2 ; pages:62-73

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.33384/26587270.2019.02.008e

Katalog-ID:	DOAJ066777844

Internformat


LEADER	01000caa a22002652 4500
001	DOAJ066777844
003	DE-627
005	20230309063423.0
007	cr uuu---uuuuu
008	230228s2020 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.33384/26587270.2019.02.008e \|2 doi
035			\|a (DE-627)DOAJ066777844
035			\|a (DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng \|a rus
100	0		\|a Goldfarb L.G. \|e verfasserin \|4 aut
245	1	0	\|a Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)
264		1	\|c 2020
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures.
650		4	\|a republic of sakha (yakutia)
650		4	\|a autosomal dominant spinocerebellar ataxia type 1 (sca1)
650		4	\|a atxn1 gene
650		4	\|a trinucleotide repeat expansion
653		0	\|a History (General) and history of Europe
653		0	\|a D
653		0	\|a Medicine
653		0	\|a R
700	0		\|a Platonov F.A. \|e verfasserin \|4 aut
773	0	8	\|i In \|t Сибирские исследования \|d Сибирские исследования, 2021 \|g 2(2020), 2, Seite 62-73 \|w (DE-627)1789694604 \|x 26587270 \|7 nnns
773	1	8	\|g volume:2 \|g year:2020 \|g number:2 \|g pages:62-73
856	4	0	\|u https://doi.org/10.33384/26587270.2019.02.008e \|z kostenfrei
856	4	0	\|u https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 \|z kostenfrei
856	4	0	\|u https://siberes.ru/gallery/SCA_1_en.pdf \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/2658-7181 \|y Journal toc \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/2658-7270 \|y Journal toc \|z kostenfrei
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_DOAJ
912			\|a GBV_ILN_11
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2086
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4392
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 2 \|j 2020 \|e 2 \|h 62-73

Indexfelder

author_variant	g l gl p f pf
matchkey_str	article:26587270:2020----::eeiietfctociiafaueadrvlnefpncrblaaait
hierarchy_sort_str	2020
publishDate	2020
allfields	10.33384/26587270.2019.02.008e doi (DE-627)DOAJ066777844 (DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664 DE-627 ger DE-627 rakwb eng rus Goldfarb L.G. verfasserin aut Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures. republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion History (General) and history of Europe D Medicine R Platonov F.A. verfasserin aut In Сибирские исследования Сибирские исследования, 2021 2(2020), 2, Seite 62-73 (DE-627)1789694604 26587270 nnns volume:2 year:2020 number:2 pages:62-73 https://doi.org/10.33384/26587270.2019.02.008e kostenfrei https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 kostenfrei https://siberes.ru/gallery/SCA_1_en.pdf kostenfrei https://doaj.org/toc/2658-7181 Journal toc kostenfrei https://doaj.org/toc/2658-7270 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2086 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4392 GBV_ILN_4700 AR 2 2020 2 62-73
spelling	10.33384/26587270.2019.02.008e doi (DE-627)DOAJ066777844 (DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664 DE-627 ger DE-627 rakwb eng rus Goldfarb L.G. verfasserin aut Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures. republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion History (General) and history of Europe D Medicine R Platonov F.A. verfasserin aut In Сибирские исследования Сибирские исследования, 2021 2(2020), 2, Seite 62-73 (DE-627)1789694604 26587270 nnns volume:2 year:2020 number:2 pages:62-73 https://doi.org/10.33384/26587270.2019.02.008e kostenfrei https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 kostenfrei https://siberes.ru/gallery/SCA_1_en.pdf kostenfrei https://doaj.org/toc/2658-7181 Journal toc kostenfrei https://doaj.org/toc/2658-7270 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2086 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4392 GBV_ILN_4700 AR 2 2020 2 62-73
allfields_unstemmed	10.33384/26587270.2019.02.008e doi (DE-627)DOAJ066777844 (DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664 DE-627 ger DE-627 rakwb eng rus Goldfarb L.G. verfasserin aut Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures. republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion History (General) and history of Europe D Medicine R Platonov F.A. verfasserin aut In Сибирские исследования Сибирские исследования, 2021 2(2020), 2, Seite 62-73 (DE-627)1789694604 26587270 nnns volume:2 year:2020 number:2 pages:62-73 https://doi.org/10.33384/26587270.2019.02.008e kostenfrei https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 kostenfrei https://siberes.ru/gallery/SCA_1_en.pdf kostenfrei https://doaj.org/toc/2658-7181 Journal toc kostenfrei https://doaj.org/toc/2658-7270 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2086 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4392 GBV_ILN_4700 AR 2 2020 2 62-73
allfieldsGer	10.33384/26587270.2019.02.008e doi (DE-627)DOAJ066777844 (DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664 DE-627 ger DE-627 rakwb eng rus Goldfarb L.G. verfasserin aut Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures. republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion History (General) and history of Europe D Medicine R Platonov F.A. verfasserin aut In Сибирские исследования Сибирские исследования, 2021 2(2020), 2, Seite 62-73 (DE-627)1789694604 26587270 nnns volume:2 year:2020 number:2 pages:62-73 https://doi.org/10.33384/26587270.2019.02.008e kostenfrei https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 kostenfrei https://siberes.ru/gallery/SCA_1_en.pdf kostenfrei https://doaj.org/toc/2658-7181 Journal toc kostenfrei https://doaj.org/toc/2658-7270 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2086 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4392 GBV_ILN_4700 AR 2 2020 2 62-73
allfieldsSound	10.33384/26587270.2019.02.008e doi (DE-627)DOAJ066777844 (DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664 DE-627 ger DE-627 rakwb eng rus Goldfarb L.G. verfasserin aut Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures. republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion History (General) and history of Europe D Medicine R Platonov F.A. verfasserin aut In Сибирские исследования Сибирские исследования, 2021 2(2020), 2, Seite 62-73 (DE-627)1789694604 26587270 nnns volume:2 year:2020 number:2 pages:62-73 https://doi.org/10.33384/26587270.2019.02.008e kostenfrei https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 kostenfrei https://siberes.ru/gallery/SCA_1_en.pdf kostenfrei https://doaj.org/toc/2658-7181 Journal toc kostenfrei https://doaj.org/toc/2658-7270 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2086 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4392 GBV_ILN_4700 AR 2 2020 2 62-73
language	English Russian
source	In Сибирские исследования 2(2020), 2, Seite 62-73 volume:2 year:2020 number:2 pages:62-73
sourceStr	In Сибирские исследования 2(2020), 2, Seite 62-73 volume:2 year:2020 number:2 pages:62-73
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion History (General) and history of Europe D Medicine R
isfreeaccess_bool	true
container_title	Сибирские исследования
authorswithroles_txt_mv	Goldfarb L.G. @@aut@@ Platonov F.A. @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	1789694604
id	DOAJ066777844
language_de	englisch russisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ066777844</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309063423.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.33384/26587270.2019.02.008e</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ066777844</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield><subfield code="a">rus</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Goldfarb L.G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">republic of sakha (yakutia)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">autosomal dominant spinocerebellar ataxia type 1 (sca1)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">atxn1 gene</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">trinucleotide repeat expansion</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">History (General) and history of Europe</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">D</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Platonov F.A.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Сибирские исследования</subfield><subfield code="d">Сибирские исследования, 2021</subfield><subfield code="g">2(2020), 2, Seite 62-73</subfield><subfield code="w">(DE-627)1789694604</subfield><subfield code="x">26587270</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:2</subfield><subfield code="g">year:2020</subfield><subfield code="g">number:2</subfield><subfield code="g">pages:62-73</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.33384/26587270.2019.02.008e</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://siberes.ru/gallery/SCA_1_en.pdf</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2658-7181</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2658-7270</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2086</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4326</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4392</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">2</subfield><subfield code="j">2020</subfield><subfield code="e">2</subfield><subfield code="h">62-73</subfield></datafield></record></collection>
author	Goldfarb L.G.
spellingShingle	Goldfarb L.G. misc republic of sakha (yakutia) misc autosomal dominant spinocerebellar ataxia type 1 (sca1) misc atxn1 gene misc trinucleotide repeat expansion misc History (General) and history of Europe misc D misc Medicine misc R Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)
authorStr	Goldfarb L.G.
ppnlink_with_tag_str_mv	@@773@@(DE-627)1789694604
format	electronic Article
delete_txt_mv	keep
author_role	aut aut
collection	DOAJ
remote_str	true
illustrated	Not Illustrated
issn	26587270
topic_title	Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion
topic	misc republic of sakha (yakutia) misc autosomal dominant spinocerebellar ataxia type 1 (sca1) misc atxn1 gene misc trinucleotide repeat expansion misc History (General) and history of Europe misc D misc Medicine misc R
topic_unstemmed	misc republic of sakha (yakutia) misc autosomal dominant spinocerebellar ataxia type 1 (sca1) misc atxn1 gene misc trinucleotide repeat expansion misc History (General) and history of Europe misc D misc Medicine misc R
topic_browse	misc republic of sakha (yakutia) misc autosomal dominant spinocerebellar ataxia type 1 (sca1) misc atxn1 gene misc trinucleotide repeat expansion misc History (General) and history of Europe misc D misc Medicine misc R
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	Сибирские исследования
hierarchy_parent_id	1789694604
hierarchy_top_title	Сибирские исследования
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)1789694604
title	Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)
ctrlnum	(DE-627)DOAJ066777844 (DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664
title_full	Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)
author_sort	Goldfarb L.G.
journal	Сибирские исследования
journalStr	Сибирские исследования
lang_code	eng rus
isOA_bool	true
recordtype	marc
publishDateSort	2020
contenttype_str_mv	txt
container_start_page	62
author_browse	Goldfarb L.G. Platonov F.A.
container_volume	2
format_se	Elektronische Aufsätze
author-letter	Goldfarb L.G.
doi_str_mv	10.33384/26587270.2019.02.008e
author2-role	verfasserin
title_sort	genetic identification, clinical features and prevalence of spinocerebellar ataxia type 1 in sakha republic (yakutia)
title_auth	Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)
abstract	Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures.
abstractGer	Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures.
abstract_unstemmed	Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2086 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4392 GBV_ILN_4700
container_issue	2
title_short	Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)
url	https://doi.org/10.33384/26587270.2019.02.008e https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 https://siberes.ru/gallery/SCA_1_en.pdf https://doaj.org/toc/2658-7181 https://doaj.org/toc/2658-7270
remote_bool	true
author2	Platonov F.A.
author2Str	Platonov F.A.
ppnlink	1789694604
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.33384/26587270.2019.02.008e
up_date	2024-07-03T21:56:58.954Z
_version_	1803596667510849536
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ066777844</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309063423.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.33384/26587270.2019.02.008e</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ066777844</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ4d4460f2b8e3489f9982971237dd0664</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield><subfield code="a">rus</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Goldfarb L.G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">republic of sakha (yakutia)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">autosomal dominant spinocerebellar ataxia type 1 (sca1)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">atxn1 gene</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">trinucleotide repeat expansion</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">History (General) and history of Europe</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">D</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Platonov F.A.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Сибирские исследования</subfield><subfield code="d">Сибирские исследования, 2021</subfield><subfield code="g">2(2020), 2, Seite 62-73</subfield><subfield code="w">(DE-627)1789694604</subfield><subfield code="x">26587270</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:2</subfield><subfield code="g">year:2020</subfield><subfield code="g">number:2</subfield><subfield code="g">pages:62-73</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.33384/26587270.2019.02.008e</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://siberes.ru/gallery/SCA_1_en.pdf</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2658-7181</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2658-7270</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2086</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4326</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4392</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">2</subfield><subfield code="j">2020</subfield><subfield code="e">2</subfield><subfield code="h">62-73</subfield></datafield></record></collection>
score	7.402793

Nicht das Richtige dabei?

Schreiben Sie uns!

Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?