Human MAGEA9 ELISA Matched Antibody Pair

Spermatogenic failure characterized by impaired sperm production is a commonmultifactorial disease with molecular and cytogenetic causes for its extreme phenotype that include azoospermia and severe oliogzoospermia. Recently, a high-resolution array-comparative genomic hybridization analysis of the X chromosome and a subsequent cohort study revealed three X-linked microdeletions (CNV64, CNV67, and CNV69) that were associated with decreased sperm production in a mixed group that included Spanish and Italian males. To confirm their spermatogenic effect, we examined the hemizygous deletions and copy dosage of the MAGE family member A9 (MAGEA9) gene, which is a potential X-linked candidate for the CNV67-related spermatogenic phenotype, to investigate their associationwith spermatogenic failure in 1722 Hanmales from southwest China. The individuals in this group consisted of 884 patients with idiopathic azoospermia/oliogzoospermia and 838 controls with normozoospermia. Our results showed that both CNV64 and CNV69 were more common in patients than in controls. Similar to that reported previously, the CNV67 was also identified as being specific to spermatogenic failure in our population, although it was rare. More importantly, the paralog ratio tests and sequence family variant analyses provided evidence that the CNV67 might cause a partial deletion of the proximal copy of the MAGEA9 and suggests that CNV67-related spermatogenic failure may be attributed to the functional defect of the Cancer/ Testis gene. Our findings highlight the potential of the Xq-linked CNV67 to serve as a novel detection target in the etiological diagnosis of spermatogenic failure and male infertility, although its pathogenic mechanism remains to be elucidated.

Genomic rearrangements are a well-recognized cause of genetic disease and can be formed by a variety of mechanisms. We report a complex rearrangement causing severe hemophilia A, identified and further characterized using a range of PCR-based methods, and confirmed using array-comparative genomic hybridization (array-CGH). This rearrangement consists of a 15.5-kb deletion/16-bp insertion located 0.6 kb from a 28.1-kb deletion/263-kb insertion at Xq28 and is one of the most complex rearrangements described at a DNA sequence level. We propose that the rearrangement was generated by distinct but linked cellular responses to double strand breakage, namely break-induced replication (13111) and a novel model of break-induced serial replication slippage (SRS). The copy number of several genes is affected by this rearrangement, with deletion of part of the Factor VIII gene (F8, causing hemophilia A) and the FUNDC2 gene, and duplication of the TMEM185A, HSFXl, MAGEA9, and MAGEA11 genes. As the patient exhibits no clinically detectable phenotype other than hemophilia A, it appears that the biological effects of the other genes involved are not dosage. dependent. This investigation has provided novel insights into processes of DNA repair including BIR and the first description of SRS during repair in a pathological context. Hum Mutat 28(12), 1198-1206, 2007. (c) 2007 Wiley-Liss, Inc.