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Extended Y chromosome haplotypes resolve multiple and unique lineages of the Jewish priesthood.

ABSTRACT: It has been known for over a decade that a majority of men who self report as members of the Jewish priesthood (Cohanim) carry a characteristic Y chromosome haplotype termed the Cohen Modal Haplotype (CMH). The CMH has since been used to trace putative Jewish ancestral origins of various populations. However, the limited number of binary and STR Y chromosome markers used previously did not provide the phylogenetic resolution needed to infer the number of independent paternal lineages that are encompassed within the Cohanim or their coalescence times. Accordingly, we have genotyped 75 binary markers and 12 Y-STRs in a sample of 215 Cohanim from diverse Jewish communities, 1,575 Jewish men from across the range of the Jewish Diaspora, and 2,099 non-Jewish men from the Near East, Europe, Central Asia, and India. While Cohanim from diverse backgrounds carry a total of 21 Y chromosome haplogroups, 5 haplogroups account for 79.5% of Cohanim Y chromosomes. The most frequent Cohanim lineage (46.1%) is marked by the recently reported P58 T->C mutation, which is prevalent in the Near East. Based on genotypes at 12 Y-STRs, we identify an extended CMH on the J-P58* background that predominates in both Ashkenazi and non-Ashkenazi Cohanim and is remarkably absent in non-Jews. The estimated divergence time of this lineage based on 17 STRs is 3,190 +/- 1,090 years. Notably, the second most frequent Cohanim lineage (J-M410*, 14.4%) contains an extended modal haplotype that is also limited to Ashkenazi and non-Ashkenazi Cohanim and is estimated to be 4.2 +/- 1.3 ky old. These results support the hypothesis of a common origin of the CMH in the Near East well before the dispersion of the Jewish people into separate communities, and indicate that the majority of contemporary Jewish priests descend from a limited number of paternal lineages.

SUBMITTER: Hammer MF

PROVIDER: S-EPMC2771134 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Extended Y chromosome haplotypes resolve multiple and unique lineages of the Jewish priesthood.

Hammer Michael F MF Behar Doron M DM Karafet Tatiana M TM Mendez Fernando L FL Hallmark Brian B Erez Tamar T Zhivotovsky Lev A LA Rosset Saharon S Skorecki Karl K

Human genetics 20090808 5

It has been known for over a decade that a majority of men who self report as members of the Jewish priesthood (Cohanim) carry a characteristic Y chromosome haplotype termed the Cohen Modal Haplotype (CMH). The CMH has since been used to trace putative Jewish ancestral origins of various populations. However, the limited number of binary and STR Y chromosome markers used previously did not provide the phylogenetic resolution needed to infer the number of independent paternal lineages that are en ...[more]

PMID: 19669163

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Project description:To determine the relationship between highly-conserved extended-haplotypes (CEHs) in the major histocompatibility complex (MHC) and MS-susceptibility.Among the ~200 MS-susceptibility regions, which are known from genome-wide analyses of single nucleotide polymorphisms (SNPs), the MHC accounts for roughly a third of the currently explained variance and the strongest MS-associations are for certain Class II alleles (e.g., HLA-DRB1*15:01; HLA-DRB1*03:01; and HLA-DRB1*13:03), which frequently reside on CEHs within the MHC.Autosomal SNPs (441,547) from 11,376 MS cases and 18,872 controls in the WTCCC dataset were phased. The most significant MS associated SNP haplotype was composed of 11 SNPs in the MHC Class II region surrounding the HLA-DRB1 gene. We also phased alleles at the HLA-A, HLA-C, HLA-B, HLA-DRB1, and HLA-DQB1 loci. This data was used to probe the relationship between CEHs and MS susceptibility.We phased a total of 59,884 extended haplotypes (HLA-A, HLA-C, HLA-B, HLA-DRB1, HLA-DQB1 and SNP haplotypes) from 29,942 individuals. Of these, 10,078 unique extended haplotypes were identified. The 10 most common CEHs accounted for 22% (13,302) of the total. By contrast, the 8,446 least common extended haplotypes also accounted for approximately 20% (12,298) of the total. This extreme frequency-disparity among extended haplotypes necessarily complicates interpretation of reported disease-associations with specific HLA alleles. In particular, the HLA motif HLA-DRB1*15:01~HLA-DQB1*06:02 is strongly associated with MS risk. Nevertheless, although this motif is almost always found on the a1 SNP haplotype, it can rarely be found on others (e.g., a27 and a36), and, in these cases, it seems to have no apparent disease-association (OR = 0.7; CI = 0.3-1.3 and OR = 0.7; CI = 0.2-2.2, respectively). Furthermore, single copy carriers of the a1 SNP-haplotype without this HLA motif still have an increased disease risk (OR = 2.2; CI = 1.2-3.8). In addition, even among the set of CEHs, which carry the Class II motif of HLA-DRB1*15:01~HLA-DQB1*06:02~a1, different CEHs have differing strengths in their MS-associations.The MHC in diverse human populations consists, primarily, of a very small collection of very highly-selected CEHs. Our findings suggest that the MS-association with the HLA-DRB1*15:01~HLA-DQB1*06:02 haplotype may be due primarily to the combined attributes of the CEHs on which this particular HLA-motif often resides.

Project description:BACKGROUND:While discrimination takes multiple forms, racial or ethnic discrimination is a root cause of this health-damaging social phenomenon. We drew on intersectionality theory, which offers an account of discrimination's multiple effects, to consider associations between women's experiences of discrimination and postpartum depression (PPD) using four measures: single forms of discrimination (SFD); multiple forms of discrimination (MFD); ethnic discrimination combined with MFD (E-MFD); and a composite MFD that interacted with women's identity (C-MFD). METHODS:We interviewed a stratified sample of 1128 mothers face to face in 2014-2015 during mothers' visits to maternal and child health clinics. The mothers belonged to three groups in Israel: Palestinian-Arab minority, Jewish immigrant, and non-immigrant Jewish. We conducted unadjusted and adjusted logistic regressions for PPD, measured on the Edinburgh Postnatal Depression Scale, in associations with SFD (experiencing discrimination based on any of the following: age, sex, class, ethno-national identity, religiosity level and skin color); MFD (experiencing 0,1, 2 or ≥ 3 of SFD); E-MFD (ethnic discrimination combined with other MFD); and finally, C-MFD (interaction between MFD and women's identity). RESULTS:Palestinian-Arab mothers had higher PPD and reported higher SFD (based on ethnicity, religiosity level, and socioeconomic status), as well as higher MFD and E-MFD. This was followed by Jewish immigrant mothers, and lastly by non-immigrant Jewish mothers. However, both MFD and E-MFD had a strong association with PPD among non-immigrant Jewish mothers reporting 2MFD and ≥ 3MFD, and Palestinian-Arab mothers reporting ≥3MFD, but no significant association among immigrant Jewish mothers. When we used C-MFD, we found a dose-response association in which Palestinian-Arab mothers experiencing more MFD (2MFD and ≥ 3MFD) were more likely to experience PPD. This was followed by immigrant Jewish mothers (reporting 2MFD and ≥ 3MFD), and lastly by non-immigrant Jewish mothers. CONCLUSIONS:MFD should be considered in relation to women's identity (being part of a minority, immigrant, or non-immigrant majority group) in maternal mental health research and practice. Otherwise, we risk underestimating the effects of MFD on PPD, especially in minority and immigrant mothers, who are more likely to face interlocking forms of discrimination.

Dataset Information

Extended Y chromosome haplotypes resolve multiple and unique lineages of the Jewish priesthood.

Publications

Extended Y chromosome haplotypes resolve multiple and unique lineages of the Jewish priesthood.

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