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Thread: Thousands of Qatari genomes inform human migration history (Discussion)

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    Thousands of Qatari genomes inform human migration history (Discussion)

    Thousands of Qatari genomes inform human migration history and improve imputation of Arab haplotypes
    Rozaimi Mohamad Razali, Juan Rodriguez-Flores, Mohammadmersad Ghorbani, Haroon Naeem, Waleed Aamer, Elbay Aliyev, Ali Jubran, Qatar Genome Program Research Consortium, Andrew G. Clark, Khalid A. Fakhro & Younes Mokrab
    Abstract
    Arab populations are largely understudied, notably their genetic structure and history. Here we present an in-depth analysis of 6,218 whole genomes from Qatar, revealing extensive diversity as well as genetic ancestries representing the main founding Arab genealogical lineages of Qahtanite (Peninsular Arabs) and Adnanite (General Arabs and West Eurasian Arabs). We find that Peninsular Arabs are the closest relatives of ancient hunter-gatherers and Neolithic farmers from the Levant, and that founder Arab populations experienced multiple splitting events 12–20 kya, consistent with the aridification of Arabia and farming in the Levant, giving rise to settler and nomadic communities. In terms of recent genetic flow, we show that these ancestries contributed significantly to European, South Asian as well as South American populations, likely as a result of Islamic expansion over the past 1400 years. Notably, we characterize a large cohort of men with the ChrY J1a2b haplogroup (n = 1,491), identifying 29 unique sub-haplogroups. Finally, we leverage genotype novelty to build a reference panel of 12,432 haplotypes, demonstrating improved genotype imputation for both rare and common alleles in Arabs and the wider Middle East.
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    Assignment of mitochondrial DNA and chromosome Y haplogroups (Qatari)

    Assignment of mitochondrial DNA and chromosome Y haplogroups
    A version of GATK supporting haploid chromosome calling (based on v3.4)64 was used to call SNPs and Indels from mitochondrial DNA (mtDNA) and chromosome Y (Chr Y) for all QGP samples (n = 6216) and QGP males only (n = 2687), respectively. SNPs only were retained for downstream analysis. Multiallelic sites were split and variants with missingness levels > 1% were excluded. mtDNA haplogroup assignments were made using HaploGrep v2.1.2071 which relies on PhyloTree catalog build 1772. Chr Y assignments were made using yhaplo v1.0.18 (https://github.com/23andMe/yhaplo) which uses reference haplogroups from the International Society of Genetic Genealogy73.

    Identification sub-haplogroups for Chr Y J1a2b haplogroup
    In order to further characterize the set of 1426 samples that were assigned to J1a2b haplogroup, we run RaxML v8.0 which performs Maximum-likelihood based phylogenetic inference74. For that, we focused on a 10-Mb region on Chr Y known to be amenable to analysis based on short read sequencing, excluding singletons and SNPs with missingness levels >1%75,76. vcf2phylip v2.3 (https://github.com/edgardomortiz/vcf2phylip) was used to convert VCF to FASTA format which was used as input to run RaxML using 100 rapid bootstrap searches and 10 maximum likelihood searches.

    Clusters within the resulting phylogenetic tree were defined using ClusterPicker v1.2.377 by applying multiple genetic distance cut-offs ranging from 1 × 10−5 to 4 × 10−3. The lower and upper boundaries of this range produced the maximum and minimum number of non-singleton clusters, respectively. Branches supported by Bootstrap values <0.9 were collapsed. Trees were plotted using iTOL 9 (https://itol.embl.de).

    For each genetic distance cut-off, informative SNPs fixated to individual clusters were identified by calculating FST score using a version of vcftools that supports haploid genotypes (v.0.14)65 and selecting SNPs with FST = 1.

    A haplogroup was defined for each non-singleton cluster as the list of SNPs with FST = 1 and AF = 1 in the respective cluster.

    Lineage dating for each haplogroup was calculated using the method of Poznik et al.78, which takes into account the number of SNPs for a given haplogroup, mutation rate and average number of years per human generation. Statistical significance of difference in estimated date of divergence of sub-haplogoups between pairs of QGP subpopulation groups was calculated using Wilcoxon Rank Sum/Mann Whitney Test.


    Description of Additional Supplementary Files
    File Name: Supplementary Data 1
    Description: List of SNPs defining novel sun-haplogroups of the J1a2b Chr Y haplogroup. Subhaplogroups were defined based on clusters with size > 10 generated by applying 5x10-4 genetic
    distance threshold on Maximum Likelihood tree with 90% bootstrapping.

    First few lines of the spreadsheet
    Y 13888354 G T - -
    Y 13934697 C T - -
    Y 13944412 A C rs373178560 -
    Y 14022682 C A rs751613702 -
    Y 14026627 T C rs868594529 -
    Y 14048450 C G - -
    Y 14065698 T C rs867384348 -
    ...
    Last edited by pmokeefe; 10-12-2021 at 09:08 PM.
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    Data availability statement:

    Access to the genotypic data used for this study and the imputation panel is through a dedicated portal by QGP (Accession ID: QF-QGP-RES-PUB-007). The informed consent given by the study participants does not cover posting of participant level phenotype and genotype data of Qatar Biobank (QB/Qatar Genome Project (QGP) in public databases. Access to QBB/QGP data can be obtained through an established ISO-certified process by submitting a project request at https://www.qatarbiobank.org.qa/research/how-apply which is subject to approval by the QBB IRB committee. Other datasets used in this study are from 1000 Genomes Project (ftp://ftp.1000genomes.ebi.ac.uk/vol1/ftp/), The Human Origin project (https://reich.hms.harvard.edu/datasets), the Greater Middle East study (GME, n = 731) (http://www.ncbi.nlm.nih.gov/projects...hs000288.v1.p1) as well as previously published whole genomes of Qataris (n = 105) (http://www.ncbi.nlm.nih.gov/Traces/s...RP061463&go=go). Source data are provided with this paper.
     
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    Quote Originally Posted by leorcooper19 View Post
    Data availability statement:

    Access to the genotypic data used for this study and the imputation panel is through a dedicated portal by QGP (Accession ID: QF-QGP-RES-PUB-007). The informed consent given by the study participants does not cover posting of participant level phenotype and genotype data of Qatar Biobank (QB/Qatar Genome Project (QGP) in public databases. Access to QBB/QGP data can be obtained through an established ISO-certified process by submitting a project request at https://www.qatarbiobank.org.qa/research/how-apply which is subject to approval by the QBB IRB committee. Other datasets used in this study are from 1000 Genomes Project (ftp://ftp.1000genomes.ebi.ac.uk/vol1/ftp/), The Human Origin project (https://reich.hms.harvard.edu/datasets), the Greater Middle East study (GME, n = 731) (http://www.ncbi.nlm.nih.gov/projects...hs000288.v1.p1) as well as previously published whole genomes of Qataris (n = 105) (http://www.ncbi.nlm.nih.gov/Traces/s...RP061463&go=go). Source data are provided with this paper.
    I'm not optimistic they'll share the new results with us, but I didn't realize there were already 105 Qatari genomes available on NCBI. We might be able to get these to David at least.
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    They don't show the Y-DNA SNPs in the article, only the list of J1a2b Chr Y haplogroup. Quite frustrating how they wrote the article because Qatar is part of the Arabian or Persian Gulf and they have different ancient substrates in their population. Of course the J1 basal structure can be generally and superficially observed in Fig. 6: Chr Y but they don't show or allow the reading of the fine resolution they have found there.
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    I am confused by their fig 1: https://www.nature.com/articles/s414...87-y/figures/1

    Does this mean that Finnish and Europeans have recent Qatari ancestry?

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    They found U9. It's really so rare, hope these are uploaded on Yfull. On another note, I am surprised how long these ROH segments are. Not sure what that Cyan admixture throughout implies, something Basal?
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    Quote Originally Posted by Max_H View Post
    I am confused by their fig 1: https://www.nature.com/articles/s414...87-y/figures/1

    Does this mean that Finnish and Europeans have recent Qatari ancestry?
    I don't think so, and I don't find it clear either. But they seem to not a clear mind about what they found anyway:
    "Indigenous Arabs were shown to form an outgroup to non-Africans and have little Neanderthal ancestry, suggesting their migration out of Africa instead of back to Africa9. Evidence from ancient human DNA suggested that the earliest populations of the Near East (which overlaps with contemporary Middle East), were derived from a Basal Eurasian lineage with minor Neanderthal admixture, and populated Anatolia, Levant and Iran prior to spreading to Europe, East Africa and Eurasian Stepp, respectively10. Iranian farmers arrived in Western Mediterranean by the Bronze age, during which this region was populated by a mix of Iranian, Steppe and North African ancestries11. The exact relationship between modern Arabs and the early founders of the ancient Near East remains unclear."

    BTW, I would like to have a more detailled analysis in terms of ancient DNA on:
    " Previous studies using hundreds of subjects gave insight to the history of these populations and impact of high consanguinity and tribalism on the prevalence of genetic diseases"
    Did high consanguinity has one or several effect on the analysis we can make about ancestral origins and split from other populations? I tend to think we should be able to see a difficulty to date a split in some cases, but else?
    Last edited by ffoucart; 10-13-2021 at 01:03 PM.

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    Quote Originally Posted by ffoucart View Post
    I don't think so, and I don't find it clear either. But they seem to not a clear mind about what they found anyway:
    "Indigenous Arabs were shown to form an outgroup to non-Africans and have little Neanderthal ancestry, suggesting their migration out of Africa instead of back to Africa9. Evidence from ancient human DNA suggested that the earliest populations of the Near East (which overlaps with contemporary Middle East), were derived from a Basal Eurasian lineage with minor Neanderthal admixture, and populated Anatolia, Levant and Iran prior to spreading to Europe, East Africa and Eurasian Stepp, respectively10. Iranian farmers arrived in Western Mediterranean by the Bronze age, during which this region was populated by a mix of Iranian, Steppe and North African ancestries11. The exact relationship between modern Arabs and the early founders of the ancient Near East remains unclear."

    BTW, I would like to have a more detailled analysis in terms of ancient DNA on:
    " Previous studies using hundreds of subjects gave insight to the history of these populations and impact of high consanguinity and tribalism on the prevalence of genetic diseases"
    Did high consanguinity has one or several effect on the analysis we can make about ancestral origins and split from other populations? I tend to think we should be able to see a difficulty to date a split in some cases, but else?
    For what is worth, I have seen many recent papers even for East Asia with odd ADMIXTURE outputs. Maybe ADMIXTURE is not a very reliable program, especially if populations with high drift are used.

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    The paper in question says: "Indigenous Arabs ... have little Neanderthal ancestry, suggesting their migration out of Africa instead of back to Africa" bur this migration could be back to Africa if it were from a population with little Neanderthal ancestry like the affines of the hypothetical Basal Eurasians.

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