Degeneracy in human multicopy RBM (YRRM), a candidate spermatogenesis gene

Area of Science:

• Genetics
• Molecular Biology
• Reproductive Medicine

Background:

• The Y-linked RNA-binding motif (RBM) genes are multicopy genes implicated in male fertility.
• Sequence variations and differing SRGY motif copy numbers exist within these gene copies.
• Mutations in the RNA-binding domain could impact protein function and male reproductive health.

Purpose of the Study:

• To identify mutations in multicopy RBM genes associated with male infertility.
• To determine the intron-exon boundaries of the YRRM 1 gene, a member of the RBM gene family.
• To analyze sequence variations within the RNA-binding domain of RBM genes.

Main Methods:

• Sequence data analysis from cDNA clones to define intron-exon boundaries.
• Single-strand conformation polymorphism (SSCP) analysis on DNA from normal and infertile men to detect mutations.
• Reverse transcription polymerase chain reaction (RT-PCR) to assess gene transcription.
• Polymerase chain reaction (PCR) followed by SSCP to map RBM gene distribution on Y Chromosome YAC contigs.

Main Results:

• YRRM 1 gene has 12 exons, with three encoding the RNA-binding domain.
• Sequence differences identified at least four gene classes, including a pseudogene and nonfunctional variants.
• All identified gene classes are transcribed, with the A class being most abundant.
• A point mutation altering the conserved RNP2 motif was found in an infertile patient and his father.
• RBM genes span a significant portion of the Y chromosome's euchromatin.

Conclusions:

• Sequence variations in RBM genes contribute to different gene classes, some nonfunctional.
• A mutation in the RBM RNA-binding domain is associated with male infertility.
• The identified mutation in the RBM gene was inherited from the father.
• Comprehensive mapping of RBM genes on the Y chromosome provides insights into their organization and potential role in male infertility.