Ulnar-Mammary Syndrome (UMS) is a congenital syndrome that is characterized by ulnar abnormalities and breast hypoplasia. The Bamshad Lab discovered that UMS is caused by mutations in the gene, TBX3. The goal of our project is to find novel TBX3 mutations that cause UMS, and expand the knowledge of how different mutations correlate to the severity of the disease. We collected DNA samples from three UMS families, and sequenced the exons of TBX3 via Sanger sequencing. Sequence analysis software allowed us to search the sequence for mutations and their locations within the gene. In the family K31928, previous screening showed that the proband and her sister, have a mutation called 1294_1301dup8. We screened the parents for mutations in TBX3, and we found that the father had the insertion mutation as well. The father’s clinical findings were very mild, but this screening confirmed that he passed the mutation causing UMS to his daughters. No mutations were found in members of the other two UMS families. The next step of this project is to investigate, in the families without TBX3 mutations, other candidate genes, as well as regulatory regions of TBX3, for mutations that could cause UMS.

Autosomal DNA, the non-recombining Y chromosome (NRY), and mitochondrial DNA (mtDNA) are all efficient means of predicting an individual's genetic ancestry. Commercially available autosomal DNA ancestry estimates are obtained using loci that show large frequency differences between continental groups known as ancestry informative markers (AIMs), and NRY and mtDNA ancestry estimates rely on haplogroup information to trace an individual's genetic lineage. Since autosomal DNA is bi-parentally inherited and the NRY and mtDNA are uni-parentally inherited, autosomal DNA potentially contains more information regarding an individual's genetic heritage than the NRY or mtDNA. Our goal is to determine the accuracy of NRY and mtDNA ancestry estimates for predicting autosomal DNA ancestry. Ancestry estimates have been obtained for 965 individuals from a global panel of human populatins from the Human Genome Diversity Project (HGDP-CEPH). Ancestry estimates were compared based on one's biogeographical ancestry or the geographic location of one's ancestors. Autosomal DNA ancestry was determined by the greatest proportion of ancestry based on seven biogeographic groups: African, European, Middle Eastern, Central/South Asian, East Asian, Oceanian, and American. Since each haplogroup is associated with a biogeographic group, the accuracy of NRY and mtDNA haplogroups in predicting autosomal DNA ancestry was determined based on a statistically signifcant number of individuals classified with their correct autosomally determined biogeographical ancestry. This information is useful to assess the quality of different ancestry estimations for use in population-based studies and direct-to-consumer ancestry tests.