47. Serendipitous identification of meiotic crossover events in struma ovarii tumors by whole genome SNP microarray analysis

Abstract

Germ cell divisions, Meiosis I and II, specifically produce haploid gametes (2n→n) required for sexual reproduction. Reciprocal crossing over between homologues of a chromosome pair is a fundamental event ensuring genomic contribution from each parent in a gamete. Using the OncoScan SNP microarray, we have identified and quantified the number and location of crossovers distributed throughout the genome. This exposure of crossovers was noted serendipitously while studying the genetic constitution of tumors of ovarian origin (struma ovarii). In tumors displaying segmental whole genome homozygosity, the precise locations of transitions from homozygosity to heterozygosity could be visualized and represent the sites of crossovers. Our analysis and data from 7 struma ovarii specimens revealed that the number of total whole genome crossovers events ranged from 41 to 99 events. Also, the total number of crossovers (summed by chromosome across these 7 struma ovarii samples) in Group A chromosomes (1–3) ranged from 23 to 41 events, in Group B (4–5) from 24 to 34 events, in Group C (6–12, X) from 17 to 25 events, in Group D (13–15) from 12 to 20 events, in Group E (16–18) from 15 to 19 events, in Group F(19–20) from 14 to 16 events, and in Group G (21–22) from 7 to 10 events. Moreover, the data revealed a) the frequency of the crossover events was directly proportional to the length of the chromosome, b) an increased (p < 0.01) number of genome-wide crossovers in the “p” arm versus the “q” arm, c) the percent homozygosity between individual chromosomes ranged between 20 and 50%, and no correlation between the percent homozygosity per chromosome, between chromosome arms, or chromosome length.