Professor, Department of Biology
Ph.D. Case Western Reserve
B.S. Stanford Univeristy
Research Interests: Genetic regulation of animal development including development of the nervous system, the mechanisms of sex determination, the origin of novel morphologies in evolution and the evolution of the vertebrate genome.
Overview: Our laboratory is interested in the genetic, genomic, and evolutionary principles that guide animal development. We investigate several aspects of this main problem:
Genome Duplication: The evolution of gene functions in development after genome duplication, focusing on skeletal development.
Fanconi anemia: A small molecule screen for compounds to rescue zebrafish Fanconi Anemia mutants as a way to identify potential therapeutics for human FA patients and to understand disease mechanisms.
MicroRNAs: The roles of microRNAs in embryonic (especially skeletal) development, including evolving miRNA functions after genome duplication.
Icefish: The genetic basis for the evolution of osteopenia or osteoporosis in Antarctic icefish.
Sex determinaion:The developmental genetic basis for sex determination in zebrafish.
Speciation: The roles of genome duplication in lineage divergence, focusing on the evolution of cis and trans acting regulation in the radiation of the danio lineage, including zebrafish, and on variation among populations of stickleback.
Oikopleura: Retaining a chordate body plan as an adult, the larvacean urochordate Oikopleura dioica represents the sister lineage to the vertebrates, diverging before the R1 and R2 rounds of genome duplication that led to the origin of vertebrate innovations.
Perchlorate toxicity and sex determination: Perchlorate is a pervasive environmental contaminant that can cause partial sex reversal in stickleback. We are investigating the hypotheses that perchlorate alters sex development through the thyroid or a non-thyroidal mechanism.
Drosophila developmental genetics: Work on Drosophila homeotic mutants, pattern formation, and ovary development.
Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.
N Engl J Med. 2018 Oct 10;:
Authors: Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, Eng CM, Esteves C, Gahl WA, Hamid R, Jacob HJ, Kikani B, Koeller DM, Kohane IS, Lee BH, Loscalzo J, Luo X, McCray AT, Metz TO, Mulvihill JJ, Nelson SF, Palmer CGS, Phillips JA, Pick L, Postlethwait JH, Reuter C, Shashi V, Sweetser DA, Tifft CJ, Walley NM, Wangler MF, Westerfield M, Wheeler MT, Wise AL, Worthey EA, Yamamoto S, Ashley EA, Undiagnosed Diseases Network
BACKGROUND: Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center. Later, a central biorepository, a metabolomics core, and a model organisms screening center were added.
METHODS: We evaluated patients who were referred to the UDN over a period of 20 months. The patients were required to have an undiagnosed condition despite thorough evaluation by a health care provider. We determined the rate of diagnosis among patients who subsequently had a complete evaluation, and we observed the effect of diagnosis on medical care.
RESULTS: A total of 1519 patients (53% female) were referred to the UDN, of whom 601 (40%) were accepted for evaluation. Of the accepted patients, 192 (32%) had previously undergone exome sequencing. Symptoms were neurologic in 40% of the applicants, musculoskeletal in 10%, immunologic in 7%, gastrointestinal in 7%, and rheumatologic in 6%. Of the 382 patients who had a complete evaluation, 132 received a diagnosis, yielding a rate of diagnosis of 35%. A total of 15 diagnoses (11%) were made by clinical review alone, and 98 (74%) were made by exome or genome sequencing. Of the diagnoses, 21% led to recommendations regarding changes in therapy, 37% led to changes in diagnostic testing, and 36% led to variant-specific genetic counseling. We defined 31 new syndromes.
CONCLUSIONS: The UDN established a diagnosis in 132 of the 382 patients who had a complete evaluation, yielding a rate of diagnosis of 35%. (Funded by the National Institutes of Health Common Fund.).
PMID: 30304647 [PubMed - as supplied by publisher]