The Developmental Genome Anatomy Project (DGAP) has been a groundbreaking initiative funded by the National Institutes of Health (NIH) through the National Institute of General Medical Sciences (NIGMS) since its inception in 1999. DGAP focuses on utilizing naturally occurring human chromosome rearrangements that are associated with major congenital anomalies in order to pinpoint and analyze genes that play a crucial role in human development. Over the years, DGAP has leveraged various evolving genomics resources, such as an ordered BAC map of the human genome and the complete human DNA sequence, to facilitate the high-throughput identification of these critical developmental genes. This comprehensive approach has not only advanced our understanding of human genetics and developmental biology but has also laid the foundation for potential breakthroughs in the treatment and prevention of congenital anomalies.

The Morton Laboratory has a longstanding interest in the genetic basis for development of uterine leiomyomata, both from the perspective of somatic changes present in tumors and from genetic variants that predispose some women to develop these tumors.  We have explored somatic events through positional cloning of genomic regions involved in cytologically visible chromosomal rearrangements, and used cytogenetic subgroups to stratify tumors for expression profiling.  Through our ongoing study, Finding Genes for Fibroids, we have recently identified seven linkage peaks in a cohort of white women.  In addition, we have identified an additional region of the genome of interest through performing a genome-wide association analysis in the Women’s Genome Health Study; this result has been replicated in an analysis of white women in an Australian cohort.  Currently, our efforts are focused on recruiting black women for both cytogenetic analyses of tumors to address somatic events in this population and for participation in our efforts to identify predisposition alleles.  To learn more about our fibroids research, please visit our Center for Uterine Fibroids website.

In our hearing and deafness research, we are interested in identifying and characterizing genes involved in the biology of hearing that when mutated underlie heritable deafness.  My laboratory identified COCH in the human deafness and vestibular disorder DFNA9 and has pursued various studies including development of a mouse model to address an understanding of the role of COCH in the pathobiology of DFNA9.  We created a human fetal cochlear cDNA library from which a collection of cochlear ESTs was made available publicly for gene discovery efforts.  In addition to investigations of cochlear genes from this library, we have also annotated hearing genes in the human genome by identifying genes disrupted or dysregulated at chromosomal breakpoints in individuals with hearing loss. Current research includes the study of copy number variants etiologic in human deafness and genome wide association studies for presbycusis.