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Articles by G. W Montgomery
Total Records ( 2 ) for G. W Montgomery
  J. E Craig , A. W Hewitt , A. E McMellon , A. K Henders , L Ma , L Wallace , S Sharma , K. P Burdon , P. M Visscher , G. W Montgomery and S. MacGregor
 

Genome-wide association studies (GWAS) have now successfully identified important genetic variants associated with many human traits and diseases. The high cost of genotyping arrays in large data sets remains the major barrier to wider utilization of GWAS. We have developed a novel method in which whole blood from cases and controls, respectively, is pooled prior to DNA extraction for genotyping. We demonstrate proof of principle by clearly identifying the associated variants for eye color, age-related macular degeneration, and pseudoexfoliation syndrome in cohorts not previously studied. Blood pooling has the potential to reduce GWAS cost by several orders of magnitude and dramatically shorten gene discovery time. This method has profound implications for translation of modern genetic approaches to a multitude of diseases and traits yet to be analyzed by GWAS, and will enable developing nations to participate in GWAS.

  M. J Prodoehl , N Hatzirodos , H. F Irving Rodgers , Z. Z Zhao , J. N Painter , T. E Hickey , M. A Gibson , W. E Rainey , B. R Carr , H. D Mason , R. J Norman , G. W Montgomery and R. J. Rodgers
 

Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-β-binding proteins (LTBP) and thereby control the bioactivity of TGFβs. TGFβs stimulate fibroblast replication and collagen production. The PCOS ovarian phenotype includes increased stromal collagen and expansion of the ovarian cortex, features feasibly influenced by abnormal fibrillin expression. To examine a possible role of fibrillins in PCOS, particularly FBN3, we undertook tagging and functional single nucleotide polymorphism (SNP) analysis (32 SNPs including 10 that generate non-synonymous amino acid changes) using DNA from 173 PCOS patients and 194 controls. No SNP showed a significant association with PCOS and alleles of most SNPs showed almost identical population frequencies between PCOS and control subjects. No significant differences were observed for microsatellite D19S884. In human PCO stroma/cortex (n = 4) and non-PCO ovarian stroma (n = 9), follicles (n = 3) and corpora lutea (n = 3) and in human ovarian cancer cell lines (KGN, SKOV-3, OVCAR-3, OVCAR-5), FBN1 mRNA levels were approximately 100 times greater than FBN2 and 200–1000-fold greater than FBN3. Expression of LTBP-1 mRNA was 3-fold greater than LTBP-2. We conclude that FBN3 appears to have little involvement in PCOS but cannot rule out that other markers in the region of chromosome 19p13.2 are associated with PCOS or that FBN3 expression occurs in other organs and that this may be influencing the PCOS phenotype.

 
 
 
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