Sequence Variants in FMR1 Sample Clauses

Sequence Variants in FMR1. Through the use of pooled-template MPS, we sequenced FMR1 in 963 developmentally delayed males, each to an average sequence depth of 130-fold coverage. As shown in Table 4.2, we identified 59 known polymorphisms in FMR1 in this population. Among these were two variants, c.-418_-417insGGC and c.18G>T, which had previously been identified in intellectually disabled patients with normal FMRP expression (Gronskov et al. 1998; Mila et al. 2000). The other 57 known variants are included in dbSNP (build 130). Providing evidence of the sensitivity of pooled-template MPS, the only FMR1 SNPs catalogued in dbSNP that we did not detect were those with low or unknown population frequencies, which were likely not present in our patient population. Additionally, we detected 130 variants in FMR1 which, to our knowledge, have not previously been reported. None are catalogued in dbSNP, nor were they detected in the first nine publicly available personal genomes (Levy et al. 2007; Bentley et al. 2008; Xxxx 2008; Xxxx et al. 2008c; Xxxxxxx et al. 2008; Ahn et al. 2009). Among these variants, 63.1% were only detected in one individual, while 36.9% were detected in multiple individuals. The majority of the novel variants were found in the introns of FMR1. However, novel sequence variants were detected in all regions of the gene. A full summary of the sequence variants detected is shown in Table 4.3.