Development and implementation of a novel panel consisting 20 markers for the detection of genetic causes of male infertility

Abstract

Azoospermia factor (AZF) genes are involved in spermatogenesis. Deletions in the region of these genes have been recognised as a major genetic cause of infertility due to defects in spermatogenesis. Klinefelter syndrome (KS) is the other main cause of male infertility. This study was performed to establish a novel method for the detection of genetic causes of infertility in males and also to investigate the prevalence, extent and position of Y chromosome microdeletions in Iranian infertile men. We developed a newly designed panel of fluorescent multiplex-PCR method to amplify 20 markers (15 sequence-tagged sites (STSs) markers which are placed in the Y chromosome AZF region, 2 short tandem repeats (STRs) and 3 segmental duplications (SDs)). This multifunctional method is for the simultaneous detection of Y chromosome microdeletions and KS. Among 149 studied infertile men, one was detected to suffer from KS and seven (4.7%) were detected with the presence of one or more deleted STS loci. The main cause of infertility for the remaining patients would be nongenetic factors. This strategy is represented as a fast and accurate method to determine the frequencies of different AZF microdeletions which are suitable for use in clinical purposes.

Diagnosis of geneticforms of azoospermia

“…Male infertility is a polyetiological disease [1], which may be due to genetic factors. Genetic abnormalities are available azoospermia in 30-50% of patients [5,6,8].…”

“…Male infertility is a polyetiological disease [1], which may be due to genetic factors. Genetic abnormalities are available azoospermia in 30-50% of patients [5,6,8].It is known that there are several genetic causes of male infertility: chromosomal disruptions (Robertson translocations, structural changes in the karyotype, inversions); abnormal number of chromosomes (chromosomal disomy, development of Klinefelter syndrome); the appearance of fallen chromosomal sites (deletions) in the AZF locus of the Y chromosome; microdeletions and point mutations in the androgen receptor (AR) gene; abnormalities in the structure of sex chromosomes (local mutations) [3,4].…”

Caracterização molecular e classificação funcional de novos padrões de expressão génica e de RNA não codificadores no tecido testicular de homens com infertilidade genética ou idiopática

“…No entanto, é possível que um homem portador do rearranjo possa ter descendência devido ao fenótipo de hipoespermatogenese, porém existe uma alta possibilidade que os filhos portadores desenvolvam infertilidade primária (Peter H. Vogt et al, 2017). Por isto, são desenvolvidas novas metodologias utilizando PCR em tempo real (Alechine & Corach, 2014), MLPA (Dutta et al, 2020), análise de fragmentos (Bahrami Zadegan et al, 2018) e microarranjos de DNA (Yuen et al, 2014).…”