Molecular Characterization of a Polymorphic 3-Mb Deletion at Chromosome Yp11.2 Containing the AMELY Locus in Singapore and Malaysia Populations

Overview

Journal Hum Genet

Specialty Genetics

Date 2007 Jun 26

PMID 17588179

Citations 13

Authors

Rita Y Y Yong

Linda S H Gan

Yuet Meng Chang

Eric P H Yap

Affiliations

Soon will be listed here.

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 approximately 13.5 +/- 3.1 kyears and approximately 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.

Citing Articles

Analysis of a Yp11.2 region deletion in a Chinese female with Turner syndrome: A case report.

Lai L, Huang X, Mei D, Li Y, Wu Y Heliyon. 2023; 9(4):e15162.

PMID: 37089332 PMC: 10113852. DOI: 10.1016/j.heliyon.2023.e15162.

A novel mutation at the AMEL primer binding region on the Y chromosome in AMELY negative male.

Takayama T Int J Legal Med. 2022; 136(2):519-526.

PMID: 35076748 DOI: 10.1007/s00414-022-02781-6.

The Y chromosome and its use in forensic DNA analysis.

Syndercombe Court D Emerg Top Life Sci. 2021; 5(3):427-441.

PMID: 34533187 PMC: 8457770. DOI: 10.1042/ETLS20200339.

Molecular characterization of the Yp11.2 region deletion in the Chinese Han population.

Pang Q, Lin Q, Wang D, Sun Z, Wang J Int J Legal Med. 2021; 135(4):1351-1358.

PMID: 33903958 PMC: 8205872. DOI: 10.1007/s00414-021-02596-x.

Alternatives to amelogenin markers for sex determination in humans and their forensic relevance.

Dash H, Rawat N, Das S Mol Biol Rep. 2020; 47(3):2347-2360.

PMID: 31983014 DOI: 10.1007/s11033-020-05268-y.

References

Cinnioglu C, King R, Kivisild T, Kalfoglu E, Atasoy S, Cavalleri G . Excavating Y-chromosome haplotype strata in Anatolia. Hum Genet. 2003; 114(2):127-48. DOI: 10.1007/s00439-003-1031-4. View

. A nomenclature system for the tree of human Y-chromosomal binary haplogroups. Genome Res. 2002; 12(2):339-48. PMC: 155271. DOI: 10.1101/gr.217602. View

Bernstein R, Wadee A, Rosendorff J, Wessels A, Jenkins T . Inverted Y chromosome polymorphism in the Gujerati Muslim Indian population of South Africa. Hum Genet. 1986; 74(3):223-9. DOI: 10.1007/BF00282538. View

Yong R, Gan L, Coble M, Yap E . Polymorphism studies of four miniSTR loci for three ethnic populations in Singapore. Leg Med (Tokyo). 2007; 9(5):278-81. DOI: 10.1016/j.legalmed.2007.01.008. View

Roffey P, Eckhoff C, Kuhl J . A rare mutation in the amelogenin gene and its potential investigative ramifications. J Forensic Sci. 2000; 45(5):1016-9. View

Zhivotovsky L, Underhill P, Cinnioglu C, Kayser M, Morar B, Kivisild T . The effective mutation rate at Y chromosome short tandem repeats, with application to human population-divergence time. Am J Hum Genet. 2003; 74(1):50-61. PMC: 1181912. DOI: 10.1086/380911. View

Feuk L, Carson A, Scherer S . Structural variation in the human genome. Nat Rev Genet. 2006; 7(2):85-97. DOI: 10.1038/nrg1767. View

Akane A, Shiono H, Matsubara K, Nakahori Y, Seki S, Nagafuchi S . Sex identification of forensic specimens by polymerase chain reaction (PCR): two alternative methods. Forensic Sci Int. 1991; 49(1):81-8. DOI: 10.1016/0379-0738(91)90174-h. View

Jobling M, Tyler-Smith C . The human Y chromosome: an evolutionary marker comes of age. Nat Rev Genet. 2003; 4(8):598-612. DOI: 10.1038/nrg1124. View

10.

Kashyap V, Sahoo S, Sitalaximi T, Trivedi R . Deletions in the Y-derived amelogenin gene fragment in the Indian population. BMC Med Genet. 2006; 7:37. PMC: 1458324. DOI: 10.1186/1471-2350-7-37. View

11.

Mathias N, Bayes M, Tyler-Smith C . Highly informative compound haplotypes for the human Y chromosome. Hum Mol Genet. 1994; 3(1):115-23. DOI: 10.1093/hmg/3.1.115. View

12.

Nakahori Y, Takenaka O, NAKAGOME Y . A human X-Y homologous region encodes "amelogenin". Genomics. 1991; 9(2):264-9. DOI: 10.1016/0888-7543(91)90251-9. View

13.

Bosch E, Lee A, Calafell F, Arroyo E, Henneman P, de Knijff P . High resolution Y chromosome typing: 19 STRs amplified in three multiplex reactions. Forensic Sci Int. 2002; 125(1):42-51. DOI: 10.1016/s0379-0738(01)00627-2. View

14.

Shen P, Lavi T, Kivisild T, Chou V, Sengun D, Gefel D . Reconstruction of patrilineages and matrilineages of Samaritans and other Israeli populations from Y-chromosome and mitochondrial DNA sequence variation. Hum Mutat. 2004; 24(3):248-60. DOI: 10.1002/humu.20077. View

15.

Santos F, Pandya A, Tyler-Smith C . Reliability of DNA-based sex tests. Nat Genet. 1998; 18(2):103. DOI: 10.1038/ng0298-103. View

16.

Parkin E, Kraayenbrink T, Opgenort J, van Driem G, Tuladhar N, de Knijff P . Diversity of 26-locus Y-STR haplotypes in a Nepalese population sample: isolation and drift in the Himalayas. Forensic Sci Int. 2006; 166(2-3):176-81. PMC: 2627361. DOI: 10.1016/j.forsciint.2006.05.007. View

17.

Vogt P, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F . Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet. 1996; 5(7):933-43. DOI: 10.1093/hmg/5.7.933. View

18.

Reiter L, Hastings P, Nelis E, De Jonghe P, Van Broeckhoven C, Lupski J . Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients. Am J Hum Genet. 1998; 62(5):1023-33. PMC: 1377084. DOI: 10.1086/301827. View

19.

Skaletsky H, Kuroda-Kawaguchi T, Minx P, Cordum H, Hillier L, Brown L . The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 2003; 423(6942):825-37. DOI: 10.1038/nature01722. View

20.

Edgar R . MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004; 32(5):1792-7. PMC: 390337. DOI: 10.1093/nar/gkh340. View