Stacey Bolk
Case Western Reserve University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Stacey Bolk.
Nature Genetics | 2000
David Altshuler; Joel N. Hirschhorn; Mia Klannemark; Cecilia M. Lindgren; Marie-Claude Vohl; James Nemesh; Charles R. Lane; Stephen F. Schaffner; Stacey Bolk; Carl Brewer; Tiinamaija Tuomi; Daniel Gaudet; Thomas J. Hudson; Mark J. Daly; Leif Groop; Eric S. Lander
Genetic association studies are viewed as problematic and plagued by irreproducibility. Many associations have been reported for type 2 diabetes, but none have been confirmed in multiple samples and with comprehensive controls. We evaluated 16 published genetic associations to type 2 diabetes and related sub-phenotypes using a family-based design to control for population stratification, and replication samples to increase power. We were able to confirm only one association, that of the common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ (PPARγ) with type 2 diabetes. By analysing over 3,000 individuals, we found a modest (1.25-fold) but significant (P=0.002) increase in diabetes risk associated with the more common proline allele (∼85% frequency). Moreover, our results resolve a controversy about common variation in PPARγ. An initial study found a threefold effect, but four of five subsequent publications failed to confirm the association. All six studies are consistent with the odds ratio we describe. The data implicate inherited variation in PPARγ in the pathogenesis of type 2 diabetes. Because the risk allele occurs at such high frequency, its modest effect translates into a large population attributable risk—influencing as much as 25% of type 2 diabetes in the general population.
Nature | 2001
David Reich; Michele Cargill; Stacey Bolk; James S. Ireland; Pardis C. Sabeti; Daniel J. Richter; Thomas Lavery; Rose Kouyoumjian; Shelli F. Farhadian; Ryk Ward; Eric S. Lander
With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting ‘haplotypes’ descended from single, ancestral chromosomes. The size of LD blocks has been the subject of considerable debate. Computer simulations and empirical data have suggested that LD extends only a few kilobases (kb) around common SNPs, whereas other data have suggested that it can extend much further, in some cases greater than 100 kb. It has been difficult to obtain a systematic picture of LD because past studies have been based on only a few (1–3) loci and different populations. Here, we report a large-scale experiment using a uniform protocol to examine 19 randomly selected genomic regions. LD in a United States population of north-European descent typically extends 60 kb from common alleles, implying that LD mapping is likely to be practical in this population. By contrast, LD in a Nigerian population extends markedly less far. The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000–53,000 years ago.
American Journal of Human Genetics | 1999
Stacey Bolk; Erik G. Puffenberger; James R. Hudson; D. Holmes Morton; Aravinda Chakravarti
We are very indebted to the members of the numerous families with nephrotic syndrome, for sharing information and donating tissue samples; without these families this work would have been impossible. We gratefully acknowledge the superb assistance of Jennifer Scott, for family studies; Kimberly Bentley, Andrew Wong, and Gilbert Wong, for DNA sequencing and technical assistance; and Carl Kashuk, for informatics. This work was supported by National Institutes of Health grant HD28088 to A.C.
American Journal of Medical Genetics | 1996
Stacey Bolk; Misha Angrist; Stuart Schwartz; Jean M. Silvestri; Debra E. Weese-Mayer; Aravinda Chakravarti
Congenital central hypoventilation syndrome (CCHS) usually occurs as an isolated phenotype. However, 16% of the index cases are also affected with Hirschsprung disease (HSCR). Complex segregation analysis suggests that CCHS is familial and has the same inheritance pattern with or without HSCR. We postulate that alteration of normal function of the receptor tyrosine kinase, RET, may contribute to CCHS based on RETs expression pattern and the identification of RET mutations in HSCR patients. To further explore the nature of the inheritance of CCHS, we have undertaken two main routes of investigation: cytogenetic analysis and mutation detection. Cytogenetic analysis of metaphase chromosomes showed normal karyotypes in 13 of the 14 evaluated index cases; one index case carried a familial pericentric inversion on chromosome 2. Mutation analysis showed no sequence changes unique to index cases, as compared to control individuals, and as studied by single strand conformational polymorphism (SSCP) analysis of the coding region of RET. We conclude that point mutations in the RET coding region cannot account for a substantial fraction of CCHS in this patient population, and that other candidate genes involved in neural crest cell differentiation and development must be considered.
Oncogene | 1998
Misha Angrist; Stacey Bolk; Kimberly Bentley; Sudha Nallasamy; Marc K. Halushka; Aravinda Chakravarti
Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most frequent cause of congenital bowel obstruction. Germline mutations in the RET receptor tyrosine kinase have been shown to cause HSCR. Mice that carry null alleles for RET or for its ligand, glial cell line-derived neurotrophic factor (GDNF), both exhibit complete intestinal aganglionosis and renal defects. Recently, the Src homology 2 (SH2) domain-containing protein Grb10 has been shown to interact with RET in vitro and in vivo, early in development. We have confirmed the map location of GRB10 on human chromosome 7, isolated human BACs containing the gene, elucidated its genomic structure, isolated a highly polymorphic microsatellite marker adjacent to exon 14 and scanned the gene for mutations in a large panel of HSCR patients. No evidence of linkage was detected in HSCR kindreds and no mutations were found in patients. These data suggest that while GRB10 may be important for signal transduction in developing embryos, it does not play an obvious role in HSCR.
Nature Genetics | 1996
Misha Angrist; Stacey Bolk; Marc K. Halushka; Paul A. Lapchak; Aravinda Chakravarti
Human Molecular Genetics | 1994
Erik G. Puffenberger; Erick R.Kauffman; Stacey Bolk; Tara C. Matise; Sarah S. Washington; Misha Angrist; Jean Weissenbach; Kenneth L. Garver; Maria J. Mascari; Roger L. Ladda; Susan A.SIaugenhaupt; Aravinda Chakravarti
Human Molecular Genetics | 1995
Misha Angrist; Stacey Bolk; Bonnie Thiel; Erik G. Puffenberger; Robert M. W. Hofstra; Charles H.C.M. Buys; D. T. Cass; Aravinda Chakravarti
Proceedings of the National Academy of Sciences of the United States of America | 2000
Joel N. Hirschhorn; Pamela Sklar; Kerstin Lindblad-Toh; Yin-Mei Lim; Melisa Ruiz-Gutierrez; Stacey Bolk; Bradley Langhorst; Steven Schaffner; Ellen Winchester; Eric S. Lander
Proceedings of the National Academy of Sciences of the United States of America | 2000
Stacey Bolk; Anna Pelet; Robert M. W. Hofstra; Misha Angrist; Rémi Salomon; David Croaker; Charles H.C.M. Buys; Stanislas Lyonnet; Aravinda Chakravarti