Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Geometrics morphometrics and fragmented archaeological skeleton remains: Examples, limits and perspectives

Though the use of geometrics morphometrics analysis is wide spread since at least 15 years in the scope of biological and anthropological sciences, the overwhelming majority of archaeologists still investigate the morphology of animal remains by the way of traditional measurements and basic statistical methods. This is at least partly due to the high level of dissociation and fragmentation of the archaeological skeletal remains. In order to estimate more precisely the limitation made by bone fragmentation and to try to take more advantage from the morphology of vertebrates’ archaeological bones, we experimented successively more and more sophisticated morphometric methods: Log Shape Ratio analyses applied to traditional length measurements (historical times in Europe; Neolithic equids of Iran), Landmark analyses (Late Glacial Equids of Western Europe), Outline analyses (Mediterranean house mouse). These different examples will be briefly presented, and assessed in terms of efficiency with reference to traditional archaeozoological measurements. General conclusions emphasize the high benefit that archaeozoology can get from a separate analysis of shape and size, especially for interpopulation comparisons and phylogeographic approaches. But it also highlights the true limitations induced by the fragmentation, which may lead to bias simplistic morphological approaches and preclude some investigation such as asymmetry analyses