De novo mutations enrich the sequence diversity and carry the clue of evolutional selection. Recent studies suggest the de novo mutations could be one of the risk factors for complex diseases. We conducted a survey of de novo mutations using the whole genome sequence data but only available on the odd autosomes of Mexican American families provided by Genetic Analysis Workshop 18. We extracted 8 three-generation families who have sequencing data available from 20 large pedigrees. By comparing the known single nucleotide variants (SNVs) in dbSNP129 and the de novo variants transmitted in the Mexican American families, we were able to estimate a de novo mutation rate of 1.64(±0.42) × 10(-8) per position per haploid genome. This result is consistent with the estimates in literature that required many extensive validation efforts, such as genotyping and further resequencing. Our analysis suggests the importance of using family samples for studying rare variants.