Identification of Novel Cytogenetic Alterations and Y Chromosome Microdeletions in Infertile Males

To conduct chromosome and Yq microdeletion analyses in infertile Indian Gujarati men.

We processed blood samples from 91 infertile and 10 fertile males to identify chromosomal abnormalities and microdeletions in European Academy of Andrology (EAA) markers of the azoospermia factor (AZF) region in Y chromosome via manual karyotyping and YqPCR.

We report 4 cases of cytogenetic abnormalities and 4 cases with Yq microdeletion. We report first case of oligoasthenoteratozoospermia (OAT) with balanced t(3;12)(p21;q24) and first case of non-obstructive azoospermia with inv(6)(p21.1p11.2). Additionally, we report 2 patients diagnosed with oligoasthenozoospermia and OAT, have heteromorphism in the Y chromosome. Two azoospermic and 1 cryptozoospermic patient had the sY127 marker of AZFb region deleted. We also found deletion of the sY84 marker in AZFa region in an oligoasthenozoospermic patient.

Male factors are implicated in half of infertile cases, where cost-effective genetic testing revolves around karyotyping and Yq microdeletion polymerase chain reaction (YqPCR). Genetic abnormalities are primarily reported for chromosomes 1 and 9; however, novel abnormalities continue to be reported. There are 24 genes associated with male infertility per Male Infertility Knowledgebase (MIK) in 3p21 and 12q24.1. Of these, the DNAH1 gene has strong association with male infertility in humans. Per the MIK, 9 genes located at 6p21.1 have functional role in male fertility. sY127 marker microdeletion is associated with oligozoospermic and azoospermic males. sY84 marker microdeletion is associated with normospermic, oligozoospermic, asthenozoospermic, and azoospermic males. Our study reiterates importance of karyotyping and YqPCR in the diagnosis of male infertility.