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Molecular characterization of a polymorphic 3-Mb deletion at chromosome Yp11.2 containing the AMELY locus in Singapore and Malaysia populations

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Abstract

Amelogenin paralogs on Chromosome X (AMELX) and Y (AMELY) are commonly used sexing markers. Interstitial deletion of Yp involving the AMELY locus has previously been reported. The combined frequency of the AMELY null allele in Singapore and Malaysia populations is 2.7%, 0.6% in Indian and Malay ethnic groups respectively. It is absent among 541 Chinese screened. The null allele in this study belongs to 3 Y haplogroups; J2e1 (85.7%), F* (9.5%) and D* (4.8%). Low and high-resolution STS mapping, followed by sequence analysis of breakpoint junction confirmed a large deletion of 3 to 3.7-Mb located at the Yp11.2 region. Both breakpoints were located in TSPY repeat arrays, suggesting a non-allelic homologous recombination (NAHR) mechanism of deletion. All regional null samples shared identical breakpoint sequences according to their haplogroup affiliation, providing molecular evidence of a common ancestry origin for each haplogroup, and at least 3 independent deletion events recurred in history. The estimated ages based on Y-SNP and STR analysis were ∼13.5 ± 3.1 kyears and ∼0.9 ± 0.9 kyears for the J2e1 and F* mutations, respectively. A novel polymorphism G > A at Y-GATA-H4 locus in complete linkage disequilibrium with J2e1 null mutations is a more recent event. This work re-emphasizes the need to include other sexing markers for gender determination in certain regional populations. The frequency difference among global populations suggests it constitutes another structural variation locus of human chromosome Y. The breakpoint sequences provide further information to a better understanding of the NAHR mechanism and DNA rearrangements due to higher order genomic architecture.

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Acknowledgments

We thank the anonymised donors for samples. This project is funded by Ministry of Defence Singapore, under projects D20030317 and D20030260-R2.

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Authors and Affiliations

  1. Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive #12-00, Singapore, Singapore, 117510

    Rita Y. Y. Yong, Linda S. H. Gan & Eric P. H. Yap

  2. Department of Chemistry, Forensic DNA Laboratory, Petaling Jaya, Malaysia

    Yuet Meng Chang

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  1. Rita Y. Y. Yong
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  2. Linda S. H. Gan
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  3. Yuet Meng Chang
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  4. Eric P. H. Yap
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Correspondence to Eric P. H. Yap.

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Yong, R.Y.Y., Gan, L.S.H., Chang, Y.M. et al. Molecular characterization of a polymorphic 3-Mb deletion at chromosome Yp11.2 containing the AMELY locus in Singapore and Malaysia populations. Hum Genet 122, 237–249 (2007). https://doi.org/10.1007/s00439-007-0389-0

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