Y-DNA haplogroups predisposed diseases/disorders
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Case: infertility
D2b [8]. D2b is also associated with AZFc microdeletions [9]. However, this haplogroup is common in Japan [10] and the prevalence of microdeletions might be proportionate with prevalence of that haplotype.
The haplogroup D2b was refactored from ISOGG nomenclature in 2011, but the data is available as haplogroup D2a. Our YDHS database contains only one mutation for haplogroup D2a; namely M116.1. However, interestingly M116.1 is located inside TXLNG2P pseudogene. A recent study by Sato et al. [11] specified the haplogroup involded in azoospermia in Japanese men to be D2*.
Case: reproductive cancers
The anomalies which result in reproductive dysfunction often predispose men to the development of other urologic ailments, including prostate cancer [17]. Indeed, just as genomic instability and Y chromosome deletions contribute to infertility, both can also contribute to carcinogenesis [13, 18]. Y chromosome deletions are one of the most common genetic anomalies among prostate cancer patients [19] and include the loss of various genes, including TSPY, PRY, EIF1AY, TMSB4Y, ZFY, BPY1, KDM5D, RBMY1A1, BPY2, and SRY [20–22]. Furthermore, there is a positive association between the number of gene losses and the stage/grade of prostate cancer [22].
Furthermore, a study among men of European descent suggests that the haplogroup E1b1b1c, which is more common among Ashkenazi Jews than other Europeans, might be associated with the development of prostate cancer [30]. Interestingly, PCDH11Y is the only gene under positive selection out of the 506 Ensembl genes in YDHS and it might have a deeper role on Y haplogroup and prostate cancer related questions.
In YDHS there was only one SNP linked to haplogroup E1b1b1c, namely V6. The gene involved in this mutation is ENSG00000092377, also known as TBL1Y by the HUGO gene nomenclature committee, translating into 4 proteins (3 splice variants). The OMIM entry linked to this gene is 400,033. TBL1Y is an X-degenerate gene that is a homolog of TBL1X [23].
Case: heart disease
[...] haplogroup I is associated with a 50 % higher risk of developing coronary artery disease than other lineages [39]. Haplogroup I is a common haplogroup in the UK, second only to R1b1b2 (prevalence 14.5-17.0 %, 70.0-72.7 %, respectively; [39]).
[...] predisposition of haplogroup I to coronary artery disease seems attributable to high levels of inflammatory immune responses rather than traditional coronary risk factors (e.g. lipid profiles; [39]).
Case: autism
Y-chromosome aneuploidy is associated with a higher than average rate of autistic disorders [44], with 28.3 % of XXYY males exhibiting autism [45]. There are 568 mutations in TBL1Y stored in YDHS database but it seems that haplogroup T has the most mutations (44) for TBL1Y gene.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477006/
