Browsing by Subject "Multiple alignment calculation"

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    Bat accelerated regions identify a bat forelimb specific enhancer in the HoxD locus
    (Public Library of Science, 2016) Booker, Betty M; Friedrich, Tara; Mason, Mandy K; VanderMeer, Julia E; Zhao, Jingjing; Eckalbar, Walter L; Logan, Malcolm; Illing, Nicola; Pollard, Katherine S; Ahituv, Nadav
    Author Summary: The limb is a classic example of vertebrate homology and is represented by a large range of morphological structures such as fins, legs and wings. The evolution of these structures could be driven by alterations in gene regulatory elements that have critical roles during development. To identify elements that may contribute to bat wing development, we characterized sequences that are conserved between vertebrates, but changed significantly in the bat lineage. We then overlapped these sequences with predicted developing limb enhancers as determined by ChIP-seq, finding 166 bat accelerated sequences (BARs). Five BARs that were tested for enhancer activity in mice all drove expression in the limb. Testing the mouse orthologous sequence showed that three had differences in their limb enhancer activity as compared to the bat sequence. Of these, BAR116 was of particular interest as it is located near the HoxD locus, an essential gene complex required for proper spatiotemporal patterning of the developing limb. The bat BAR116 sequence drove robust forelimb expression but the mouse BAR116 sequence did not show enhancer activity. These experiments correspond to analyses of HoxD gene expressions in developing bat limbs, which had strong forelimb versus weak hindlimb expression for Hoxd10 - 11 . Combined, our studies highlight specific genomic regions that could be important in shaping the morphological differences that led to the development of the bat wing.
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    The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk
    (Public Library of Science, 2012) Vogelsang, Matjaz; Wang, Yabing; Veber, Nika; Mwapagha, Lamech M; Parker, M Iqbal
    The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during normal DNA metabolism or are induced by certain cancer-contributing exposures. We assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5 MMR genes and oesophageal cancer risk in South Africans. Prior to genotyping, SNPs were selected from the HapMap database, based on their significantly different genotypic distributions between European ancestry populations and four HapMap populations of African origin. In the Mixed Ancestry group, the MSH3 rs26279 G/G versus A/A or A/G genotype was positively associated with cancer (OR = 2.71; 95% CI: 1.34-5.50). Similar associations were observed for PMS1 rs5742938 (GG versus AA or AG: OR = 1.73; 95% CI: 1.07-2.79) and MLH3 rs28756991 (AA or GA versus GG: OR = 2.07; 95% IC: 1.04-4.12). In Black individuals, however, no association between MMR polymorhisms and cancer risk was observed in individual SNP analysis. The interactions between MMR genes were evaluated using the model-based multifactor-dimensionality reduction approach, which showed a significant genetic interaction between SNPs in MSH2, MSH3 and PMS1 genes in Black and Mixed Ancestry subjects, respectively. The data also implies that pathogenesis of common polymorphisms in MMR genes is influenced by exposure to tobacco smoke. In conclusion, our findings suggest that common polymorphisms in MMR genes and/or their combined effects might be involved in the aetiology of oesophageal cancer.