Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population

Risch, Neil; Leon, Deborah de; Ozelius, Laurie J.; Kramer, Patricia L.; Almasy, Laura; Singer, Burton H.; Fahn, Stanley; Breakefield, Xandra O.; Bressman, Susan

doi:10.1038/ng0295-152

Cited by 388 publications

(342 citation statements)

References 23 publications

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“…Bottlenecks or cofounder effects, which are not considered by the Island model used here to calculate the migration rate, could contribute to the elevated allele frequency in Ashkenazi. 21,22 However, bottlenecks could not alone explain the observed high frequency in Ashkenazi Jews from many different countries of origin.…”

Section: Analysis and Discussionmentioning

confidence: 99%

Evidence for recent selection of the CCR5-Δ32 deletion from differences in its frequency between Ashkenazi and Sephardi Jews

Maayan¹,

Zhang

Shinar³

et al. 2000

Genes Immun

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Recent studies have shown higher frequencies of the CCR5-⌬32 allele and the CCR5-⌬32/⌬32 genotype, which confers protection against HIV infection, in northern Europe as compared to Mediterranean countries. Here, we analyse the prevalence of CCR5-⌬32 in 922 HIV seronegative blood donors in Israel to verify its frequency in Jews of Ashkenazi and Sephardi origin. A significant difference (P Ͻ 0.001) was found between the CCR5-⌬32 allele frequency in Ashkenazi (13.8%) vs (4.9%) Jews. In contrast, no significant difference was observed in the frequency of the CCR2-64I mutation between Ashkenazi (9.2%) and Sephardi (13.4%) Jews. Using the Island model we calculate that a minimal genetic migration rate of 3% per generation would have been necessary if the higher CCR5-⌬32 prevalence in Ashkenazi is to be fully explained by mixing with the indigenous north-European populations. This putative migration rate is 20-fold higher than that currently estimated from other genes, and would correspond to a non-realistic minimal current admixture of 80%. Thus, our results suggest that a positive selection process for CCR5-⌬32 should have occurred in northern Europe at most a 1000 years ago, after the Ashkenazi Jews separated from their Sephardi kin and moved to north Europe. Genes and Immunity (2000) 1, 358-361.

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Section: Analysis and Discussionmentioning

confidence: 99%

Evidence for recent selection of the CCR5-Δ32 deletion from differences in its frequency between Ashkenazi and Sephardi Jews

Maayan¹,

Zhang

Shinar³

et al. 2000

Genes Immun

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“…Historical evidence is that growth rates have varied greatly being much slower in the distant past than in the last century. 24 Using averaged figures of a 5% growth rate and 25-year interval, we have estimated that the founder mutation arose around 6300 years ago (range 4400-8600 years). A common founder was originally proposed for Finnish FALS cases based on a 42-SNP haplotype.…”

Section: Uk:1 C C Gg C C T Gggt G G a C A T C C T A G T A C A T A A Amentioning

confidence: 99%

The C9ORF72 expansion mutation is a common cause of ALS+/−FTD in Europe and has a single founder

et al. 2012

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A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS þ / ÀFTD from five European cohorts (total n ¼ 1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n ¼ 434) and controls (n ¼ 856). Haplotypes were analysed using PLINK and aged using DMLE þ . In a London clinic cohort, the HREM was the most common mutation in familial ALS þ / ÀFTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS þ / ÀFTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, Po10 À8 ). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe.

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“…35 Estimation of the population age, origin, and population history of found the c.802-8_810del17insGC mutation were based on our results and those of previous studies in which the risk haplotype was determined in Chinese and Japanese Bietti cases. 5,22,23 The age of the mutation was estimated using three approaches, an analytical approach, 15 an iterative approach, 17 and a posterior Bayesian distribution approach as implemented in the program DMLE+2.2. 36 On the basis of their analysis of the intragenic SNP haplotypes, Lin et al previously suggested that the c.802-8_810del17insGC had a common origin in the Japanese and Chinese populations.…”

Section: Discussionmentioning

confidence: 99%

“…The mutation age was estimated as described in Equation (1) of Risch et al, 15,16 g ¼ log ðdÞ log ð1ÀyÞ , where δ is the linkage disequilibrium constant, δ = (P D − P N )/(1 − P N ), with P D being the frequency of the allele on chromosomes of mutation carriers and P N being the frequency of the allele in the control population. Genotypes of unaffected individuals were taken from the Figure 1 Gene and mutation structural predictions of the effects of the four novel missense mutations.…”

Section: Haplotype Analysis and Age Estimationmentioning

confidence: 99%

“…To examine the origin of the c.802-8_810del17insGC mutation more closely, the mutation age was estimated in the Chinese and Japanese populations using the approach described by Risch et al, 15,16 and Goldstein et al, 17 as well as Bayesian disequilibrium estimates of the marginal posterior density as instituted in the DMLE+ program. 19 A summary of these results with the age given in generations is shown in Table 4.…”

Section: Cyp4v2 Mutations X Jiao Et Almentioning

confidence: 99%

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Identification and population history of CYP4V2 mutations in patients with Bietti crystalline corneoretinal dystrophy

Jiao

Jin

et al. 2017

Eur J Hum Genet

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To identify known and novel CYP4V2 mutations in patients with Bietti crystalline cornea (BCD), expand the spectrum of CYP4V2 mutations, and characterize the population history of the c.802-8_810del17insGC mutation common in Asian populations, genomic DNA was isolated from peripheral blood samples from 58 unrelated patients with clinical diagnoses of BCD. Exons and flanking intronic regions of the CYP4V2 gene were dideoxy DNA sequenced. Nonpathogenic polymorphisms were excluded and known mutations were identified by sequencing 192 unaffected individuals from similar ethnic backgrounds and examination of online databases. The age of the c.802-8_810del17insGC mutation was estimated using three independent approaches. A total of 28 CYP4V2 mutations, 9 of which were novel, were detected in the 58 patients with BCD. These included 19 missense, 4 nonsense, 2 deletion, 2 splice site, and 1 insertion-deletion mutations. Two missense variants of uncertain significance were also detected. The age of the c.802-8_810del17insGC mutation was estimated to be 1040-8200 generations in the Chinese and 300-1100 generations in the Japanese populations. These results expand the mutation spectrum of CYP4V2, and provide insight into the origin of the c.802-8_810del17insGC mutation in the Chinese population and its transmission to the Japanese population.

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Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population

Cited by 388 publications

References 23 publications

Evidence for recent selection of the CCR5-Δ32 deletion from differences in its frequency between Ashkenazi and Sephardi Jews

Evidence for recent selection of the CCR5-Δ32 deletion from differences in its frequency between Ashkenazi and Sephardi Jews

The C9ORF72 expansion mutation is a common cause of ALS+/−FTD in Europe and has a single founder

Identification and population history of CYP4V2 mutations in patients with Bietti crystalline corneoretinal dystrophy

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