The Ashkenazic Jewish Bloom Syndrome Mutation blmAsh Is Present in Non-Jewish Americans of Spanish Ancestry

Ellis, Nathan A.; Ciocci, Susan; Proytcheva, Maria; Lennon, David; Groden, Joanna; German, James

doi:10.1086/302167

Cited by 65 publications

(51 citation statements)

References 11 publications

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“…25 in a heterozygous or homozygous state were tested for the blm Ash mutation, they were found to be negative, showing that this haplotype predated the blm Ash mutation. Our results are in agreement with previous haplotype studies (Ellis et al 1998) that showed the presence of a predominant single haplotype (based on microsatellite markers surrounding BLM) considered to be the founder haplotype that blm Ash occurred in Ashkenazi Jews.…”

Section: Pilot Association Studiessupporting

confidence: 93%

“…25) in the BLM gene, which appears to be the ancestral haplotype on which the blm Ash mutation occurred in the Ashkenazi Jewish population. Ellis et al (1998) using microsatellite data obtained similar association results. However, the stability of SNP sites offers opportunities to estimate the age of such disease mutations more precisely.…”

Section: Pilot Association Studiessupporting

confidence: 56%

“…To test the utility of the identified SNPs and predicted haplotypes, we carried out two pilot association studies. The blm Ash mutation (Ellis et al 1995) is found in ∼97% of Bloom syndrome patients of Ashkenazi Jewish origin, patients of Spanish American ancestry (Ellis et al 1998), and Jewish patients of Polish descent (Shahrabani-Gargir et al 1998). The mutation has a carrier frequency of ∼1% among Ashkenazi Jews (Roa et al 1999) and results in protein truncation due to 6-bp deletion/ 7-bp insertion in exon 10 (Ellis et al 1995).…”

Section: Pilot Association Studiesmentioning

confidence: 99%

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Complex SNP-Based Haplotypes in Three Human Helicases: Implications for Cancer Association Studies

Trikka

Fang²,

Renwick³

et al. 2002

Genome Res.

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We have initiated a candidate gene approach to study variation and predisposition to cancer in the four major ethnic groups that constitute the U.S. population (African Americans, Caucasians, Hispanics, and Asians). We resequenced portions of three helicase genes (BLM, WRN, and RECQL) identifying a total of 37 noncoding single nucleotide polymorphisms (SNPs). Haplotype inference predicted 50 haplotypes in BLM, 56 in WRN, and 47 in RECQL in a sample of 600 chromosomes. Approximately 10% of the predicted haplotypes were shared among all ethnic groups. Linkage disequilibrium and recombination effects showed that each locus has taken a diverse evolutionary path. Primate DNA analysis of the same loci revealed one human haplotype per gene shared with the great apes, indicating that the observed diversity occurred since the divergence of humans from the last common ancestor. In BLM, we confirmed the presence of a founder haplotype among Ashkenazi Jews homozygous for the blm Ash mutation. The cosegregating haplotype was seen in all (6/6) samples of Ashkenazi descent, whereas in the general population it has a low frequency (0.02) and was not found in African Americans. In WRN, ethnic samples were studied for their haplotype content and the presence or absence of six previously described coding SNPs (cSNPs). Hispanic individuals carrying two of these cSNPs showed a 60% increase in the frequency of a common haplotype (haplotype No. 28). In the pooled sample, no association was found. Because (1) the majority of the haplotypes are population specific and (2) the patterns of linkage disequilibrium, recombination, and haplotype diversity are markedly different between gene regions, these data show the importance of either ethnically matched controls or within-family-based disease-gene association studies.

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Section: Pilot Association Studiessupporting

confidence: 93%

Section: Pilot Association Studiessupporting

confidence: 56%

Section: Pilot Association Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Complex SNP-Based Haplotypes in Three Human Helicases: Implications for Cancer Association Studies

Trikka

Fang²,

Renwick³

et al. 2002

Genome Res.

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show abstract

“…Although recent converts were not legally permitted to travel to the New World, it has been argued that many in fact made the journey. Interestingly, the analysis of Y chromosome data and rare disease mutations are consistent with a genetic contribution from North Africa and the Middle East to the ancestry of Ibero-Americans (15,26,35,65,100).…”

Section: Subcontinental Ancestrymentioning

confidence: 52%

The Genetic Diversity of the Americas

Adhikari

Chacón-Duque

Mendoza‐Revilla

et al. 2017

Annu. Rev. Genom. Hum. Genet.

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The history of the Americas involved the encounter of millions of Native Americans, Europeans, and Africans. A variable admixture of these three continental groups has taken place between them throughout the continent, influenced by demography and a range of social factors. These events have had a major influence on the genetic makeup of populations across the continent. Here, we summarize the demographic history of the region, highlight some social factors that affected historical admixture, and review major patterns of diversity across the Western Hemisphere based on genetic data.2

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“…39 This suggests the possibility that contemporary Ashkenazi mtDNA diversity may derive, in part, from a small and subdivided ancestral mtDNA gene pool, and is consistent with the hypothesis that some high frequency disease alleles originated before the separation of Jewish communities in the Near East. 40,41 Indeed, estimates of the age of mutations causing Ashkenazi genetic diseases range from recent times (ie, during demographic upheavals within Europe in the past 500 years), 6,26,40,42 to times when ancestral Ashkenazi populations were first migrating to and within Europe, 43 to times before Jewish populations migrated out of the Near East. 40,44,45 …”

Section: Discussionmentioning

confidence: 99%

MtDNA evidence for a genetic bottleneck in the early history of the Ashkenazi Jewish population

et al. 2004

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The relative roles of natural selection and accentuated genetic drift as explanations for the high frequency of more than 20 Ashkenazi Jewish disease alleles remain controversial. To test for the effects of a maternal bottleneck on the Ashkenazi Jewish population, we performed an extensive analysis of mitochondrial DNA (mtDNA) hypervariable segment 1 (HVS-1) sequence and restriction site polymorphisms in 565 Ashkenazi Jews from different parts of Europe. These patterns of variation were compared with those of five Near Eastern (n ¼ 327) and 10 host European (n ¼ 849) non-Jewish populations. Only four mtDNA haplogroups (Hgs) (defined on the basis of diagnostic coding region RFLPs and HVS-1 sequence variants) account for B70% of Ashkenazi mtDNA variation. While several Ashkenazi Jewish mtDNA Hgs appear to derive from the Near East, there is also evidence for a low level of introgression from host European non-Jewish populations. HVS-1 sequence analysis revealed increased frequencies of Ashkenazi Jewish haplotypes that are rare or absent in other populations, and a reduced number of singletons in the Ashkenazi Jewish sample. These diversity patterns provide evidence for a prolonged period of low effective size in the history of the Ashkenazi population. The data best fit a model of an early bottleneck (B100 generations ago), perhaps corresponding to initial migrations of ancestral Ashkenazim in the Near East or to Europe. A genetic bottleneck followed by the recent phenomenon of rapid population growth are likely to have produced the conditions that led to the high frequency of many genetic disease alleles in the Ashkenazi population.

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The Ashkenazic Jewish Bloom Syndrome Mutation blmAsh Is Present in Non-Jewish Americans of Spanish Ancestry

Cited by 65 publications

References 11 publications

Complex SNP-Based Haplotypes in Three Human Helicases: Implications for Cancer Association Studies

Complex SNP-Based Haplotypes in Three Human Helicases: Implications for Cancer Association Studies

The Genetic Diversity of the Americas

MtDNA evidence for a genetic bottleneck in the early history of the Ashkenazi Jewish population

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