| DiGeorge syndrome is a developmental field defect of the third and fourth pharyngeal pouches. It is characterized by cardiac abnormality, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcaemia resulting from a deletion or chromosomal translocation in 22q11 so that only one copy of the normal 22nd chromosome exists. DNA sequence in this region was determined to locate the genes that are deleted or disrupted in this region as part of a pilot project in the human genome project (HGP), to test the strategy, and to develop the technologies needed to pursue the goals of the HGP. In the course of my study, I have developed and optimized technologies for plasmid and cosmid DNA isolation and implemented a new enzyme in DNA sequencing that has improved the efficiency and dramatically reduced the sequencing cost. Over a half million base pairs of human DNA were sequenced and many features in the sequence have been identified. Two break points in two DiGeorge syndrome patients also have been characterized. Analysis of this sequence data reveals two RNA genes (DGS-A and DGCR5), one transmembrane protein gene (DGS-C/LAN/DGCR2/IDD), a human clathrin heavy chain (CHC2) gene, a developmental control gene (Tbx1), a gene for a receptor of the von Willebrand factor, the platelet glycoprotein Ib beta gene, and a catechol-O-methyltransferase (COMT) gene. A new approach for building gene models was proposed and investigated, and three new gene models have been built for three new human genes that have not previously been characterized, namely, a mouse H5-like cell division control gene, a glutathione reductase-like gene and a mouse p120-like gene. Other potential gene coding regions are represented by clusters of ESTs and X-Grail predicted exons. A unique gene structure involving potential overlapping genes on the same strand is described for the first time in the human genome and additional human ubiquitous and unique repeats also have been located. Overall this half-million bases of 22q11 has a repeat sequence density of 21% and encodes at least 12 genes. |
