The critical region of overlap defining the AZFa male infertility intervalof proximal Yq contains three transcribed sequences

The position of deletion breakpoints in a series of four AZFa male infertil ity patients has been refined using new markers derived from BAC clone DNA sequence covering the AZFa male infertility interval. The proximal half of the AZFa interval is occupied by pseudogene sequences with homology to Xp22 . The distal half contains an anonymous expressed sequence tag (named AZFaT 1) found transcribed in brain, testis, and skeletal muscle and the DFFRY an d DBY genes. All the patients have AZFaT1 and DFFRY deleted in their entire ty and three patients additionally have DBY deleted. The three patients wit h AZFaT1, DFFRY, and DBY deleted show a severe Sertoli cell only syndrome t ype I phenotype, whereas the patient that has retained DBY shows a milder o ligozoospermic phenotype. The expression of DBY in a cell line from this la tter patient is unaltered; this shows that it is the loss of genes lying wi thin the deletion that is responsible for the observed oligozoospermia. RT- PCR analysis of mouse testis RNA from normal and XXSxr(a) mice (devoid of g erm cells) has shown that Dby is expressed primarily in somatic cells and t hat the level of expression is unaltered during germ cell differentiation. This contrasts with Dffry where no transcripts are detectable in XXSxr(a) m ouse testis and expression occurs specifically in testis mRNA in a germ cel l dependent fashion.