The most primitive CM chondrites, Asuka 12085, 12169, and 12236, of subtypes 3.0–2.8: Their characteristic features and classification

CM chondrites (CMs) are the most abundant group of carbonaceous chondrites. CMs experienced varying degrees of secondary aqueous alteration and heating that modified or destroyed their primitive features. We have studied three chondrites, Asuka (A) 12085, A 12169, and A 12236. Their modal compositions, chondrule size distributions, and bulk composition indicate that they are CMs. However, the common occurrence of melilite in CAIs and glass in chondrules, abundant Fe–Ni metal, the absence of tochilinite-cronstedtite intergrowths, and almost no phyllosilicates, all suggest that these chondrites, especially A 12169, experienced only minimal aqueous alteration. The textures and compositions of metal and sulfides, the lack of ferroan rims on AOA olivines, the compositional distribution of ferroan olivine, and the Raman spectra of their matrices, indicate that these chondrites experienced neither significant heating nor dehydration. These chondrites, especially A 12169, are the most primitive CMs so far reported. The degree of the alteration increases from A 12169, through A 12236, to A 12085. We propose the criteria for subtypes of 3.0–2.8 for CMs. A 12169, A 12236, and A 12085 are classified as subtype 3.0, 2.9, and 2.8, respectively. The oxygen isotopic composition of the Asuka CMs is consistent with these samples having experienced only a limited degree of aqueous alteration. The CM and CO groups are probably not derived from a single heterogeneous parent body. These chondrites are also of particular significance in view of the imminent return of sample material from the asteroids Ryugu and Bennu

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

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers