The Efficiency of Type-Specific High-Risk Human Papillomavirus Models in the Triage of Women with Atypical Squamous Cells of Undetermined Significance.

PURPOSE: To evaluate the performance of different high-risk human papillomavirus (HR-HPV) genotype models in triaging women with cytological diagnosis of atypical squamous cells of undetermined significance (ASCUS). PATIENTS AND METHODS: A total of 36,679 Chinese women who underwent cytology and HR-HPV genotyping assessments during cervical cancer screening were enrolled in this study. Women with cytology-proven ASCUS were referred for further screening by colposcopy and biopsy. The study endpoint was histological detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) at any of the follow-up visits. The sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of different HR-HPV genotype combination models were estimated. RESULTS: In all, 1675 (4.9%) women were identified as having ASCUS, 1454 women underwent colposcopy and biopsy, and 6.0% (87/1454) women were identified as having CIN2+ lesions. Among those with ASCUS who were identified as having CIN2+, the HR-HPV infection rate was 97.7%, and the prevalence rates of HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 were 48.3%, 8.0%, 6.9%, 4.6%, 1.1%, 2.3%, 3.4%, 3.4%, 26.4%, 1.1%, 17.2%, 2.3%, 0.0% and 0.0%, respectively. Compared to other HR-HPV-type combination models, the HPV16/18/31/33/52/58 model achieved a higher sensitivity [93.1 (87.8-98.4)], specificity [73.0 (70.7-75.4)], PPV [18.0 (14.5-21.5)], NPV [99.4 (98.9-99.9)], PLR [3.7 (3.1-3.8)] and NLR [0.06 (0.03-0.18)] for the triage of ASCUS patients, but the colposcopy referral rate (30.9%) was significantly lower than that of the recommended HR-HPV model (44.0%). CONCLUSION: This study confirms that the specific HR-HPV genotype HPV16/18/31/33/52/58 is an alternative strategy for ASCUS triage and can effectively reduce the high burden of colposcopy referrals in China.

Genome-wide copy number variant analysis reveals variants associated with 10 diverse production traits in Holstein cattle.

BACKGROUND: Copy number variation (CNV) is an important type of genetic variation contributing to phenotypic differences among mammals and may serve as an alternative molecular marker to single nucleotide polymorphism (SNP) for genome-wide association study (GWAS). Recently, GWAS analysis using CNV has been applied in livestock, although few studies have focused on Holstein cattle. RESULTS: We describe 191 CNV detected using intensity data from over 700,000 SNP genotypes generated with the BovineHD Genotyping BeadChip (Illumina, San Diego, CA) in 528 Holstein cows. The CNV were used for GWAS analysis of 10 important production traits of 473 cattle related to feed intake, milk quality, and female fertility, as well as 2 composite traits of net merit and productive life. In total, we detected 57 CNV associated (P < 0.05 after false discovery rate correction) with at least one of the 10 phenotypes. Focusing on feed efficiency and intake-related phenotypes of residual feed intake and dry matter intake, we detected a single CNV associated with both traits which overlaps a predicted olfactory receptor gene OR2A2 (LOC787786). Additionally, 2 CNV within the RXFP4 (relaxin/insulin like family peptide receptor 4) and 2 additional olfactory receptor gene regions, respectively, were associated with residual feed intake. The RXFP4 gene encodes a receptor for an orexigenic peptide, insulin-like peptide 5 produced by intestinal L cells, which is expressed by enteric neurons. Olfactory receptors are critical for transmitting the effects of odorants, contributing to the sense of smell, and have been implicated in participating in appetite regulation. CONCLUSIONS: Our results identify CNV for genomic evaluation in Holstein cattle, and provide candidate genes, such as RXFP4, contributing to variation in feed efficiency and feed intake-related traits. These results indicate potential novel targets for manipulating feed intake-related traits of livestock.

Strong and stable geographic differentiation of swamp buffalo maternal and paternal lineages indicates domestication in the China/Indochina border region.

The swamp type of the Asian water buffalo is assumed to have been domesticated by about 4000 years BP, following the introduction of rice cultivation. Previous localizations of the domestication site were based on mitochondrial DNA (mtDNA) variation within China, accounting only for the maternal lineage. We carried out a comprehensive sampling of China, Taiwan, Vietnam, Laos, Thailand, Nepal and Bangladesh and sequenced the mtDNA Cytochrome b gene and control region and the Y-chromosomal ZFY, SRY and DBY sequences. Swamp buffalo has a higher diversity of both maternal and paternal lineages than river buffalo, with also a remarkable contrast between a weak phylogeographic structure of river buffalo and a strong geographic differentiation of swamp buffalo. The highest diversity of the swamp buffalo maternal lineages was found in south China and north Indochina on both banks of the Mekong River, while the highest diversity in paternal lineages was in the China/Indochina border region. We propose that domestication in this region was later followed by introgressive capture of wild cows west of the Mekong. Migration to the north followed the Yangtze valley as well as a more eastern route, but also involved translocations of both cows and bulls over large distances with a minor influence of river buffaloes in recent decades. Bayesian analyses of various migration models also supported domestication in the China/Indochina border region. Coalescence analysis yielded consistent estimates for the expansion of the major swamp buffalo haplogroups with a credibility interval of 900 to 3900 years BP. The spatial differentiation of mtDNA and Y-chromosomal haplotype distributions indicates a lack of gene flow between established populations that is unprecedented in livestock.