A large interstitial deletion encompassing the amelogenin gene on the short arm of the Y chromosome

Abstract

Sex tests based on amelogenin are part of various PCR multiplex reaction kits widely used for human gender identification and have important applications in forensic casework, prenatal diagnosis, DNA databasing and blood sample storage. The two most common sex tests based on amelogenin are represented by primer sets that delimit a 6-bp deletion on the X chromosome to produce X/Y fragments of 106/112 or 212/218 bp, respectively. Few cases of AMELY deletion, usually considered as polymorphisms, have been reported so far and a detailed characterization of the molecular alteration is still lacking. In this study, we describe a large interstitial deletion of the Y short arm encompassing the AMELY locus in two unrelated individuals. The first case was identified in an oligozoospermic, otherwise phenotypically normal, 32-year-old man during the screening for Y microdeletions performed on a sample of infertile males. The second one was found among amniotic liquid samples tested by quantitative fluorescence-polymerase chain reaction and cytogenetic analysis for prenatal diagnosis. The extent of the deletion, spanning approximately 2.5 Mb, was better characterised by pulsed-field gel electrophoresis, followed by fluorescence in situ hybridization and STS marker analysis.

Null alleles of the X and Y chromosomal amelogenin gene in a Chinese population

“…3) revealed the absence of the DYS458 locus both in samples 4 and 5, which has been reported previously [9][10][11][12]. Using three alternative single DY458 primer sets, the specific DY458 amplicons in samples 4 and 5 were still absent (Table 3), suggesting a deletion of DY458 region rather than a point mutation at primer sites.…”

“…Deletion of the sequences on theYp11.2 region has been observed in males showing different haplotypes and haplogroups [7][8][9][10][11][12]. Lattanzi et al [9] described a large interstitial deletion spanning approximately 2.5 Mb of the Y short arm encompassing the AMELY locus in infertile males and one amniotic liquid sample for prenatal diagnosis by performing pulsed-field gel electrophoresis, followed by fluorescence in situ hybridization and sequence-tagged sites (STS) marker analysis.…”

“…Commercially available kits for genotyping short tandem repeats (STRs) usually contain the AMEL primers and have been widely used in DNA databasing, forensic casework, prenatal diagnoses, and transplantation monitoring. Several studies have reported mutations in the X or Y homologue of the AMEL gene, which could cause amplification failure of AMELX or AMELY and result in incorrect sex identification [3][4][5][6][7][8][9][10][11][12]. In the Chinese population, however, some scattered cases with AMEL gene mutations have been reported [5][6][7], although no systematic analysis of the frequency data based on large samples has been done.…”

Cell-Free RNA Is a Reliable Fetoplacental Marker in Noninvasive Fetal Sex Determination

“…Sex determination on the basis of AMELY is widely accepted in genetic diagnosis for sex determination, e.g., in the forensic field, prenatal diagnosis, and preimplantation genetic diagnosis. However, a few cases with AMELY deletion resulting in allelic dropout have been reported in different populations (21 ). The frequency of AMELY negatives is low, and ethnic differences seem to exist (0.018% in Europe, 0.02% in Australia, 1.85%-2.36% in India) (21,22 ).…”

“…However, a few cases with AMELY deletion resulting in allelic dropout have been reported in different populations (21 ). The frequency of AMELY negatives is low, and ethnic differences seem to exist (0.018% in Europe, 0.02% in Australia, 1.85%-2.36% in India) (21,22 ). In a pilot study, we have attempted to incorporate other Y chromosome genes, SRY (sex-determining region Y) and UTY (ubiquitously transcribed tetratricopeptide repeat containing, Y-linked), but found too many primer interactions in the multiplex RT-PCR (data not shown).…”