Y chromosome interstitial deletion induced Y-STR allele dropout in AMELY-negative individuals

Abstract

Short tandem repeat (STR) multiplexes with the amelogenin (AMEL) gene as a gender marker have been used as a routine tool of forensic DNA analysis. It has been reported that AMEL-based gender detection could misidentify a known male as a female due to the dropout of amelogenin Y (AMELY) allele. Other gender markers, such as Y-chromosomal short tandem repeat (Y-STR), may be a substitution of AMEL and help the sex determination. In current study, employing AmpFlSTR® Sinofiler and AmpFlSTR® Y-filer™ PCR Amplification kit, 18 AMELY-negative males were identified. Accordingly, the incidence of the AMELY dropout was 0.227 ‰ (18/79,304) in Chinese population. Sequencing of AMELY allele and analyzing of azoospermia factors region suggested that 3 out of 18 misidentifications were induced by mutations in the primer-binding region of the AMELY, while other 15 sex misidentifications were results of Y chromosome microdeletions with variant lengths. Moreover, variant combination patterns of AMELY dropout and Y-STRs deletions were also observed. Our data suggested that Y-STR locus dropout may indicate more problems, especially in the mixed sample's interpretation. Results of haplogroup prediction showed that seven AMELY dropouts combined with variant Y-STR deletions can be classified as the J2 subdivision, suggesting that some of these Y chromosomes might descend from a common ancestor.

Diversification of Pakistani Amelogenin-Y-Null Male Haplotypes

“…These findings further strengthened the concept of having fragment deletion in the Y chromosome of these individuals. Three different deletion patterns of AMEL-Y-null cases have been reported in literature: AMEL-Y-DYS456, AMEL-Y-DYS458, and AMEL-Y-DYS458-DYS522 [ 42 – 44 ]. The deletion observed in all eighteen AMEL-Y-null male samples of the Pakistani population was found to be AMEL-Y and DYS458.…”

“…ese samples were labeled as SQ-1-SQ-18. e frequency of AMEL-Y-null males in various populations has been studied and has been shown to vary in different populations ranging from 0.037 to 10% [38][39][40][41][42].…”

Analysis of the 19 Y-STR and 16 X-STR loci system in the Han population of Shandong province, China

“…When using only amelogenin as a sex marker in autosomal STR kits, dropouts in amelogenin Y or X may be troublesome in forensic caseworks during sex affirmation (Ma et al, 2012;Davis et al, 2012;Ou et al, 2012). X-STRs and Y-STRs are important complements to autosomal STR analysis in some forensic cases (Yang et al, 2016).…”

Future directions of forensic DNA databases

“…In contrast, the Amelogenin locus usually is not used in a database search. With a low dropout rate of Amelogenin-Y (eg, 0.0227% in Chinese population) (9), adding one Y-STR with relatively low discriminating power may not be the best decision to support forensic investigation leads developed through database searches.…”