印度的脊髓小脑共济失调 27B 型 (SCA27B):一项大型队列研究揭示了其古老的起源。

IF 1.6 4区 医学 Q3 CLINICAL NEUROLOGY
Neurogenetics Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI:10.1007/s10048-024-00770-y
Tiyasha De, Pooja Sharma, Bharathram Upilli, A Vivekanand, Shreya Bari, Akhilesh Kumar Sonakar, Achal Kumar Srivastava, Mohammed Faruq
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引用次数: 0

摘要

背景:印度的民族多样性为研究遗传疾病突变的起源历史提供了一个独特的机会。脊髓小脑共济失调 27B 型(SCA27B)是最近发现的一种显性遗传小脑疾病,由成纤维细胞生长因子 14(FGF14)内含子 1 中的 GAA 重复扩增引起。据报道,该病主要发生在欧洲人群中,我们的目的是筛查这一突变,并研究印度共济失调患者中 SCA27B 的始祖单倍型:方法:我们在约 1400 名未定性共济失调患者和同类患者组成的大型印度队列中进行了 GAA 重复序列筛查,并进行了基于长线程测序的 GAA 重复序列长度评估。我们还进行了基于高通量基因分型的单倍型分析。我们利用约 1000 个印度基因组来研究 GAA 高危扩增等位基因:我们报告了在未定性的印度共济失调队列中,SCA27B 的频率高达 1.83%(n = 23)。我们观察到几个双倍性 GAA 扩增突变(n = 5)的发病年龄较小。我们观察到在 FGF14-GAA 基因位点的侧翼有一个风险单倍型 (AATCCGTGG),该单倍型分布在一个 74 kb 的连锁不平衡区域。我们进一步研究了这一风险单倍型在不同地域人群中的频率。在欧洲人群中,风险单倍型的发生率最高(29.9%),其次是印度人(21.5%)。假设系谱相关,观察到的风险单倍型已存在了约 1100 代(约 22000 年):这项研究为了解 SCA27B 及其在印度次大陆上旧石器时代的起源提供了宝贵的资料。双复制扩增的高发生率可能与印度人口的内婚性质有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Spinocerebellar ataxia type 27B (SCA27B) in India: insights from a large cohort study suggest ancient origin.

Spinocerebellar ataxia type 27B (SCA27B) in India: insights from a large cohort study suggest ancient origin.

Background: The ethnic diversity of India provides a unique opportunity to study the history of the origin of mutations of genetic disorders. Spinocerebellar ataxia type 27B (SCA27B), a recently identified dominantly inherited cerebellar disorder is caused by GAA-repeat expansions in intron 1 of Fibroblast Growth Factor 14 (FGF14). Predominantly reported in the European population, we aimed to screen this mutation and study the founder haplotype of SCA27B in Indian ataxia patients.

Methods: We have undertaken screening of GAA repeats in a large Indian cohort of ~ 1400 uncharacterised ataxia patients and kindreds and long-read sequencing-based GAA repeat length assessment. High throughput genotyping-based haplotype analysis was also performed. We utilized ~ 1000 Indian genomes to study the GAA at-risk expansion alleles.

Findings: We report a high frequency of 1.83% (n = 23) of SCA27B in the uncharacterized Indian ataxia cohort. We observed several biallelic GAA expansion mutations (n = 5) with younger disease onset. We observed a risk haplotype (AATCCGTGG) flanking the FGF14-GAA locus over a 74 kb region in linkage disequilibrium. We further studied the frequency of this risk haplotype across diverse geographical population groups. The highest prevalence of the risk haplotype was observed in the European population (29.9%) followed by Indians (21.5%). The observed risk haplotype has existed through ~ 1100 generations (~ 22,000 years), assuming a correlated genealogy.

Interpretation: This study provides valuable insights into SCA27B and its Upper Paleolithic origin in the Indian subcontinent. The high occurrence of biallelic expansion is probably relevant to the endogamous nature of the Indian population.

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来源期刊
Neurogenetics
Neurogenetics 医学-临床神经学
CiteScore
3.90
自引率
0.00%
发文量
24
审稿时长
6 months
期刊介绍: Neurogenetics publishes findings that contribute to a better understanding of the genetic basis of normal and abnormal function of the nervous system. Neurogenetic disorders are the main focus of the journal. Neurogenetics therefore includes findings in humans and other organisms that help understand neurological disease mechanisms and publishes papers from many different fields such as biophysics, cell biology, human genetics, neuroanatomy, neurochemistry, neurology, neuropathology, neurosurgery and psychiatry. All papers submitted to Neurogenetics should be of sufficient immediate importance to justify urgent publication. They should present new scientific results. Data merely confirming previously published findings are not acceptable.
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