Genome-wide single nucleotide polymorphism array and whole-genome sequencing reveal the inbreeding progression of Banna minipig inbred line.

Inbred pigs are promising animal models for biomedical research and xenotransplantation. Established in 1980, the Banna minipig inbred (BMI) line originated from a sow and its own male offspring. It was selected from a small backcountry minority Lahu village, where records show that no other pig breed has ever been introduced. During the inbreeding process, we perfomed extreme inbreeding over 23 consecutive generations using full-sibling or parent-offspring mating. In order to investigate the inbreeding effects in BMI pigs across generations over the past 40 years, in this study we conducted a genome-wide SNP genotyping of the last 10 generations, representing generations 14-23. In total, we genotyped 57,746 SNPs, corresponding to an average decrease in heterozygosity rate of 0.0078 per generation. Furthermore, we were only able to identify 18,216 polymorphic loci with a MAF larger than 0.05, which is substantially lower than the values in previous reports on other pig breeds. In addition, we sequenced the genome of the first pig in the twenty-third generation (inbreeding coefficient 99.28%) to an average coverage of 12.4× to evaluate at the genome level the impact of advanced inbreeding. ROH analysis indicates that BMI pigs have longer ROHs than Wuzhishan and Duroc pigs. Those long ROH regions in BMI pigs are enriched for distinct functions compared with the highly polymorphic regions. Our study reveals a genome-wide allele diversity loss during the progress of inbreeding in BMI pigs and characterizes ROH and polymorphic regions as a result of inbreeding. Overall, our results indicate the successful establishment of the BMI line, which paves the way for further in-depth studies.

Genetic Instability in Locus rs5498 E469K (A/G) of ICAM-1 Gene in Patients with Colorectal Cancer and Breast Cancer.

Single-nucleotide polymorphism rs5498 E469K (A/G) in ICAM-1 gene modulates functional activity of this protein and is associated with the risk of some diseases. Tumor cell rs5498 E469K (A/G) genotypes were compared with genotypes of patients with colorectal and breast cancer, residents of the Nizhniy Novgorod region. Specimens of peripheral blood and tumor foci from patients with colorectal and breast cancer and peripheral blood specimens from normal subjects were analyzed. The frequency of genotypes of single-nucleotide rs5498 E469K (A/G) sequence in the Nizhny Novgorod population coincide with the frequency of genotypes characteristic of residents of Germany. Comparison of genotypes of peripheral blood and tumor cells from patients with colorectal and breast cancer showed loss of cancer cell heterozygosity. The frequency of heterozygosity loss increases with colorectal cancer progress from one stage to another.

Loss of multi-sites allde heterozygosity on chromosome 9 in esophageal carcinoma / 肿瘤研究与临床

Objective To investigate the gene variation and the dependability and to evaluate the possible tumor suppressor genes on chromosome 9 in the development and progression of EC. Methods LOH was detected in normal esophageal mucosa, high-grade squamous dysplasia and esophageal squamous cell carcinoma by microdissection, polymerase chain reaction, denaturing polyacrylamide gel eleetrophoresis and silver nitrate staining technology. The changes of LOH at six microsatellite markers and the relationship between LOH rate were analyzed. Results In the informative cases, total frequency of LOH was 17.2 % in high-grade squamous dysplasia and 24.9 % in esophageal squamous cell carcinoma. In high grade squamous dysplasia and squamous cell carcinoma, LOH was detected at marker D9S162 (20.8 %, 36.7 %), D9S171 (33.3 %, 36 %), D9S753(34.8 %, 46.2 %), D9S1748(4.2 %, 13.8 %), D9S242(14.3 %, 21.2 %), D9S43(0, 0). The frequency of LOH showed significant difference among the six microsatellite markers (X2=17.26, P< 0.005; X2=22.66,P<0.005). Conclusion The progression from normal squamous epithelium to high-grade Squamous dysplasia and subsequently to squamous cell carcinoma of the esophagus is associated with accumulation of chromosomal change. The situs of D9S171, D9S162, D9S242, D9S753 exist higher LOH and all exceed 20 %. Possible tumor suppressor genes at or near D9S171, D9S162, D9S242, D9S753 may be related to the progression of esophageal squamous cell carcinoma.

Study on loss of heterozygosity of SMAD2 in primary gastric carcinoma / 中国普通外科杂志

Objective To investigate the role of loss of heterozygosity (LOH) of SMAD2 and its relationship with clinicopathological parameters of primary gastric carcinoma. Methods Fifty cases of primary gastric carcinoma were monitored by polymerase chain reaction -single strand conformation polymorphism (PCR- SSCP) and silver staining to detect SMAD2 LOH. Results The incidence of LOH was 40.0%(22/45) at D18S450 and 33.3%(16/48)at D18S460 . LOH occurred in SMAD2 was 55.1%(27/49).The rate of SMAD2 LOH was 72.0% (18/25) in primary gastric carcinoma with lymph node metastasis , which was significantly higher than that in without lymph node metastasis (P

Loss of heterozygosity and mRNA expression at deleted in colorectal cancer gene locus in gastric cancer.

AIM: To assess the effects of the deleted in colorectal cancer (DCC) gene changes on the development and progression of gastric cancer. METHODS: The loss of heterozygosity (LOH) and mRNA expression DCC gastric cancer using a PCR-based detection method. RESULTS: LOH was found in 35.3% (18/51) of the specimens, and the LOH was more frequently detected in tumors from patients with stage III or IV cancer (50.5%) than those in stages I or II (14.3%) (P < 0.05). The occurrence of LOH was not found to correlate with the histological type, tumor size, invasion depth and lymph node metastasis of gastric cancer. The mRNA expression of the DCC gene was studied in 26 of the 51 cases, of which LOE was found in 30.8% (8/26). LOE was not significantly correlated to LOH or other clinicopathological parameters. CONCLUSION: LOH and LOE of DCC gene are frequently encountered in gastric cancer, and the LOH of DCC gene is a late event associated with progression of gastric cancer.

Preliminary study on the loss of heterozygosity at 17p13 in gastric and colorectal cancers.

AIM: To evaluate the role of p53 in the development and progression of colorectal cancer and gastric carcinoma by analyzing the loss of heterozygosity (LOH) at 17p13.1 and 17p13.3. METHODS: LOH at the p53 gene locus and 17p13.3 were examined in 22 cases of gastric carcinoma and 14 cases of colorectal cancer by Southern blot analysis. RESULTS: Of the 22 gastrocarcinoma cases, 12 (54%) were heterozygous and LOH was detected in 6 (50%) of the 12 informative cases. In the 14 colorectal cancer cases, 10 (71%) were heterozygous, and LOH was detected in 6 (60%) of the 10 informative cases. CONCLUSION: LOH at the p53 gene locus is a frequent event in multiple step carcinogenesis progression. The high frequency of LOH at 17p13.3 suggests that there may be another tumor suppresser gene in that chromosome region.