The MLH1 2101C>A (Q701K) variant increases the risk of gastric cancer in Chinese males

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is one of the most common cancers affecting East Asians, and <it>MLH1 </it>could play a critical role during tumorigenesis in this condition.</p> <p>Methods</p> <p>Samples from 236 Chinese patients suffering from gastric cancer were screened for <it>MLH1 </it>germline mutations. Carrier frequencies of the mutations were compared between gastric cancer patients and 240 cancer-free controls. Bioinformatic analysis was used to predict the effect of these mutations on protein function and mRNA splicing.</p> <p>Results</p> <p>Six <it>MLH1 </it>sequence alterations were identified in gastric cancer patients including two promoter region substitutions, -93G>A and -28A>G, and four missense mutations 649C>T (R217C), 655A>G (I219V), 1151T>A (V384D) and 2101C>A (Q701K). Compared with the <it>MLH1 </it>2101CC genotype, the 2101CA genotype was associated with a risk of gastric cancer (OR = 8.42, 95% CI = 1.04-68.06) in males. Furthermore, the <it>MLH1 </it>2101C>A mutant was predicted by <it>in silico </it>analysis to affect exon splicing ability. Immunohistochemistry of one index patient carrying the <it>MLH1 </it>2101C>A mutation demonstrated a loss of MLH1 protein and normal expression of MSH2 and E-cadherin. No significant differences were demonstrated between cases and controls for the other five <it>MLH1 </it>variants but the data indicated an ethnic difference in the frequency of these variations between Eastern Asians and Western populations.</p> <p>Conclusions</p> <p>An ethnic-specific <it>MLH1 </it>mutation spectrum occurred in Chinese gastric cancer patients. The <it>MLH1 </it>2101C>A mutation could be a marker for susceptibility to gastric cancer, particularly in males.</p

Fine mapping of the major gene BhHLS1 controlling seed size in wax gourd (Benincasa hispida)

Introduction/BackgroundThe seed size of wax gourds is an important agronomic trait; however, the associated genes have not yet been reported.MethodsIn this study, we used a high-density genetic map constructed based on F8 recombinant inbred line populations derived from a cross between MY-1 (large seed) and GX-71 (small seed) strains to detect quantitative trait locis (QTLs) for seed-size-related traits in wax gourd over a two-year period.ResultsTwo stable QTLs (qSL10 and qSW10) for seed length (SL) and seed width (SW) on chromosome 10 were repeatedly detected over two years (2021–2022). qSL10 had a phenotypic variation rate of 75.30% and 80.80% in 2021 and 2022, respectively. Whereas, qSW10 had a phenotypic variation rate of 66.60% and 73.80% in 2021 and 2022, respectively. Further, a single nucleotide polymorphism mutation was found to cause early termination of Bch10G006400 (BhHLS1) translation in GX-71 through sequencing analysis of candidate genes. Based on gene functional annotation and quantitative real-time PCR analyses, BhHLS1 encoded a probable N-acetyltransferase HLS1-like protein and its expression level was significantly different between parents. Therefore, BhHLS1 is a major candidate gene associated with a one-factor polymorphism regulating the SL and SW of wax gourds. Finally, based on variation in the BhHLS1 sequence, a cleaved amplified polymorphic sequence marker was developed for the molecular marker-assisted breeding of wax gourds.DiscussionOverall, this study is of great significance for the genetic improvement of seed size, verification of gene functions, and cultivation of specific germplasm resources for wax gourds

Development and Application of InDel Markers Linked to Fruit-Shape and Peel-Colour Genes in Wax Gourd

The wax gourd is commonly grown in many countries because of its high nutritional and economic value. While the genes for the fruit shape and peel colour of wax gourd have been reported, the InDel markers linked to these genes remain undeveloped. In this study, the InDel markers linked to fruit-shape (Bch02G016830) and peel-colour (Bch05G003950) genes were developed from resequenced data. We used 120 inbred lines, 536 isolated populations, and 4 commercial hybrids to evaluate the validity and application value of the InDel markers. The accuracy rates of nine pairs of fruit-shape InDel markers (GX1-GX9) were 84.16&ndash;91.66% in 120 inbred lines. The accuracy rates of 27 pairs of peel-colour InDel markers (PS1-PS27) within approximately 3.0 Mb upstream and 3.0 Mb downstream of the peel-colour gene were 100% and those of 6 pairs of peel-colour InDel markers (PS28-PS33) within 3.0&ndash;20 Mb upstream and downstream of the peel-colour gene were 55.83&ndash;90% in 120 inbred lines. The purity of four commercial hybrids determined using GX1, GX2, PS13, and PS14 was highly consistent with the field results for purity determination. Our results provide important information for genetic linkage map construction, molecular-marker-assisted selective breeding, and purity determination of wax gourd hybrids