Direct analysis of meiotic recombination in human trisomy 18 oocytes

EDITH CHENG, RHEA VALLENTE, DANIELLE DIPERNA, THERESA NALUAICECCHINI, TERRY HASSOLD, University of Washington, Obstetrics and Gynecology, Seattle, Washington, Washington State University, Molecular Biosciences, Pullman, Washington, University of Washington, Internal Medicine (Medical Genetics), Seattle, Washington OBJECTIVE: Direct visualization of meiotic exchanges in chromosomally normal and abnormal human oocytes was completed to conduct detailed studies on the frequency, distribution, and placement of recombination sites in aneuploid and euploid gametes. STUDY DESIGN: Oocytes from normal fetuses and a 20 week trisomy 18 fetus underwent fluorescence antibody staining (FAS) with meiotic proteins associated with synaptonemal complex formation (SCP3) and the DNA mismatch repair protein, MLH 1, that locates recombination foci. Fluoresence in situ hybridization (FISH) was completed to evaluate for chromosomespecific variations in exchange patterns. RESULTS: MLH 1 foci were present from zygotene through diplotene in chromosomally normal and abnormal meiocytes. 32 trisomy 18 and 37 chromosomally normal pachytene stage meiocytes were studied for recombination characteristics. The mean number of MLH1 foci, 39, was lower in the trisomy 18 gametes compared to 69 for the chromosomally normal gametes. MLH 1 foci location per chromosome arm on chromosomes other than chromosome 18 was similar to that of chromosomally normal oocytes. Interference was observed. CONCLUSION: This is the first report on the recombination pattern of human trisomic meiocytes. The findings suggest that recombination is disturbed and deficient in trisomic oocytes. Such disturbances might be a risk factor for oocyte atresia and could be explain the observed ovarian dysgenesis seen in trisomy 18 infants. Reduced recombination may also increase the risk for abnormal chromosome segregation leading to aneuploid gametes and provide a mechanism to explain the interchromosomal effect.