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Angela
16-10-17, 17:53
See:Variation and functional impact of Neanderthal ancestry in Western AsiaTaskent et al
https://academic.oup.com/gbe/article/doi/10.1093/gbe/evx216/4540916/Variation-and-functional-impact-of-Neanderthal

So annoying: only the abstract and some supplementary material is available. The Oxford Press is the absolute worst in this regard.

"Neanderthals contributed genetic material to modern humans via multiple admixture events. Initial admixture events presumably occurred in Western Asia shortly after humans migrated out-of-Africa. Despite being a focal point of admixture, earlier studies indicate lower Neanderthal introgression rates in some Western Asian populations as compared to other Eurasian populations. To better understand the genome-wide and phenotypic impact of Neanderthal introgression in the region, we sequenced whole genomes of 10 present-day Europeans, Africans, and the Western Asian Druze at high depth, and analyzed available whole genome data from various other populations, including 16 genomes from present-day Turkey. Our results confirmed previous observations that contemporary Western Asian populations, on average, have lower levels of Neanderthal-introgressed DNA relative to other Eurasian populations. Modern Western Asians also show comparatively high variability in Neanderthal ancestry, which may be attributed to the complex demographic history of the region. We further replicated the previously described depletion of putatively functional sequences among Neanderthal-introgressed haplotypes. Still, we find dozens of common Neanderthal-introgressed haplotypes in the Turkish sample associated with human phenotypes, including anthropometric and metabolic traits, as well as the immune response. One of these haplotypes is unusually long and harbors variants that affect the expression of members of the CCR gene family and are associated with celiac disease. Overall, our results paint a complex first picture of the genomic impact of Neanderthal introgression in the Western Asian populations."

Jovialis
16-10-17, 18:23
Here's a link to the PDF of the full version.
https://watermark.silverchair.com/evx216.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3Z L_9Cf3qfKAc485ysgAAAfYwggHyBgkqhkiG9w0BBwagggHjMII B3wIBADCCAdgGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMH AZEbdtd7jhiTmbHAgEQgIIBqRUmy8l6GJ1-bl6HzgrGrKBphvFoN2iJrkJcvTuIoiVGIKUdBMRjmOZc4j97La LNSt1shRUGT_XV6DbwPSrdzbuMVfFCc9VqMLCksCk6vDuxMVJE yGw3KgI5b75mroYN8-h9ZeB5A0NYIbN-GQDWxmBAypYgcnloihG0Oh6RtDBy1ArI_pZAsd9TUSnisNqYRQ o3_qEUHIXKFPOGesfm6rWRtEUDd7bzIGCxEP2fDJ_MFJ0W2QbY 6dsHGtuHJsL075qcC0JoIATTYFD0uzMSvqHu84LgAyXa5klnuy tf4I0ydS6hUu3wfJU8Tf2TMqeoMKnw1tf-MzhOhX6U-U-rn4orW13KJioIfoeD6mTpp2KQ0gDfwjqVUPY6w4PPgHFYICYkI N-i1_1dQWNZUCIjMHvGyumAT5wCWatBrrwkYLcr7revdB9gK41rU yOViy4Bg-F0pGwHroTDtSPN6G4JAn91tz5XcOi-yGjAgvWDiP4ZCESDsGCeHhs-E4mjtoP7Jcopo8BnG9oLvqamXzKgAA_C-fq_oWPqb5XousE0ydRXJG3snY22mIR_

Edit: looks like the session times out randomly. At any rate, I found it by googling the title of the paper, it should be the second result.

Angela
16-10-17, 18:52
Thanks a lot, Jovialis...

Good summary to begin with for newbies:
"Moreover, haplotype level scrutinization of these admixture events revealed asignificant depletion of coding sequences among haplotypes admixed fromNeanderthals, suggesting strong negative selection acting on these sequences(Sankararaman et al. 2014; Vernot and Akey 2014; Harris and Nielsen 2016; Juric et al.2016). In contrast, a small but measurable number of introgressed haplotypes havebeen adaptively maintained in the human population (Huerta-Sánchez et al. 2014;Dannemann et al. 2016; Gittelman et al. 2016; Quach et al. 2016; Racimo et al. 2017).In addition, recent studies have now shown that Neanderthal-introgressed haplotypesmight affect the expression levels of multiple genes."

Important, I think, in explaining the results:
"Specifically, recent inbreeding, migration, and local isolation may create deviations inthe clinal distribution of genetic variation in this region (Gokcumen et al. 2011; Scott etal. 2016), which may give rise to considerable heterogeneity in the levels of Neanderthalintrogression among populations." (in West Asia)

"The 3321 putatively Neanderthal-introgressed haplotypes observed in 16 Turkish genomes cover close to 280Mb (~9%) of sequence,corresponding on average to 18Mb of Neanderthal-introgressed DNA in each genome." That of course depends on whether they correctly distinguished them from just archaic sequences.

"Neanderthal haplotypes found in the Turkishpopulation are depleted for exonic sequences, where we observe that only 1.1% of theNeanderthal-introgressed haplotypes are covered by exons, as compared to theexpected 1.5% for the similar-sized regions (p<10-15, Chi-square test). This result isconsistent with the previously reported notion that there is widespread negativeselection against functional Neanderthal alleles (Harris and Nielsen 2016; Juric et al.2016)."

"18 of the 41 common GWAS variants on Neanderthal-derived haplotypes in theTurkish population were immune- and metabolism-related."

I don't know what to make of the following. Any ideas?

"The haplotype harbors rs13098911, a variant associated with celiac disease(Dubois et al. 2010). This haplotype overlaps with the C-C motif chemokine receptor(CCR) gene family with a known role in HIV infection (Choe et al. 1996). Intriguingly,other variants within the same region, which are not linked to the Neanderthalhaplotype, were associated with Behcet’s disease (Kirino et al. 2013), an autoimmunedisorder highly common in Western Asia. Collectively, its functional relevance andunusual size raise the possibility that this haplotype may have been maintained inWestern Asian populations through adaptive forces, making it an ideal candidate forfuture studies."

Or this...

"Previous studies have shown that the genes related to metabolism may have beenparticularly affected by Neanderthal-introgressed haplotypes (Khrameeva et al. 2014).Here we identified two independent Neanderthal-variants (rs13201877, rs10540)common in this Turkish sample (at ~9% and ~6% frequency, respectively) andassociated with Body Mass Index (BMI."

LeBrok
17-10-17, 16:56
"The haplotype harbors rs13098911, a variant associated with celiac disease(Dubois et al. 2010). This haplotype overlaps with the C-C motif chemokine receptor(CCR) gene family with a known role in HIV infection (Choe et al. 1996). Intriguingly,other variants within the same region, which are not linked to the Neanderthalhaplotype, were associated with Behcet’s disease (Kirino et al. 2013), an autoimmunedisorder highly common in Western Asia. Collectively, its functional relevance andunusual size raise the possibility that this haplotype may have been maintained inWestern Asian populations through adaptive forces, making it an ideal candidate forfuture studies." Positive introgression for not clear yet reason. Possibly multifunctional gene?

Or this...


"Previous studies have shown that the genes related to metabolism may have beenparticularly affected by Neanderthal-introgressed haplotypes (Khrameeva et al. 2014).Here we identified two independent Neanderthal-variants (rs13201877, rs10540)common in this Turkish sample (at ~9% and ~6% frequency, respectively) andassociated with Body Mass Index (BMI." I guess, similar situation to above.