Small extrachromosomal circular DNA harboring targeted tumor suppressor gene mutations supports intratumor heterogeneity in mouse liver cancer induced by multiplexed CRISPR/Cas9.

Background: Primary liver cancer has significant intratumor genetic heterogeneity (IGH), which drives cancer evolution and prevents effective cancer treatment. CRISPR/Cas9-induced mouse liver cancer models can be used to elucidate how IGH is developed. However, as CRISPR/Cas9 could induce chromothripsis and extrachromosomal DNA in cells in addition to targeted mutations, we wondered whether this effect contributes to the development of IGH in CRISPR/Cas9-induced mouse liver cancer.

[Analysis of flavonoids and antitumor activity of transgenic Saussurea involucrate].

The aim of this paper was to investigate the flavonoids of callus of transgenic and non-transgenic Saussurea involucrate and its antitumor activity on the esophageal cancer CaEs-17 cells. The species and content of mono-phenols were detected by high performance liquid chromatography. The growth of human esophageal cancer CaEs-17 cells was detected using CCK-8 assay, apoptosis morphology observation and flow cytometry.

MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer.

About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers.

A bootstrap-based regression method for comprehensive discovery of differential gene expressions: an application to the osteoporosis study.

Unlabelled: A common purpose of microarray experiments is to study the variation in gene expression across the categories of an experimental factor such as tissue types and drug treatments. However, it is not uncommon that the studied experimental factor is a quantitative variable rather than categorical variable. Loss of information would occur by comparing gene-expression levels between groups that are factitiously defined according to the quantitative threshold values of an experimental factor.

Identification of Las2, a major modifier gene affecting the Pas1 mouse lung tumor susceptibility locus.

Lung cancer is the leading cause of cancer death worldwide. Here, we describe a genome-wide association study of chemically induced lung tumorigenesis on 593 mice from 21 inbred strains using 115,904 genotyped and 1,952,918 imputed single nucleotide polymorphisms (SNPs). Using a genetic background-controlled genome search, we identified a novel lung tumor susceptibility gene Las2 (Lung adenoma susceptibility 2) on distal chromosome 18.

Choice of study phenotype in osteoporosis genetic research.

Osteoporosis is a common disease characterized by compromised bone strength predisposing a person to an increased risk of osteoporotic fracture (OF). Recently, extensive efforts have been made to identify candidate genes underlying osteoporosis by the use of surrogate phenotypes, such as bone mineral density (BMD) and bone geometry. Among them, BMD is a suitable choice if we aim to classify the role of biological pathways for bone strength and to understand the bone conditions in the development of osteoporosis.

Evidence for major pleiotropic effects on bone size variation from a principal component analysis of 451 Caucasian families.

Aim: To identify pleiotropic quantitative trait loci (QTL) influencing bone size (BS) at different skeletal sites in Caucasians.

Methods: In a sample containing 3899 Caucasians from 451 pedigrees, 410 microsatellite markers spaced approximately 8.9 cM apart across the human genome were genotyped.

Bivariate whole genome linkage analysis for femoral neck geometric parameters and total body lean mass.

Unlabelled: A genome-wide bivariate analysis was conducted for femoral neck GPs and TBLM in a large white sample. We found QTLs shared by GPs and TBLM in the total sample and the sex-specific samples. QTLs with potential pleiotropy were also disclosed.

Relationship of obesity with osteoporosis.

Context: The relationship between obesity and osteoporosis has been widely studied, and epidemiological evidence shows that obesity is correlated with increased bone mass. Previous analyses, however, did not control for the mechanical loading effects of total body weight on bone mass and may have generated a confounded or even biased relationship between obesity and osteoporosis.

Objective: The objective of this study was to reevaluate the relationship between obesity and osteoporosis by accounting for the mechanical loading effects of total body weight on bone mass.

A gene expression signature predicts survival of patients with stage I non-small cell lung cancer.

Background: Lung cancer is the leading cause of cancer-related death in the United States. Nearly 50% of patients with stages I and II non-small cell lung cancer (NSCLC) will die from recurrent disease despite surgical resection. No reliable clinical or molecular predictors are currently available for identifying those at high risk for developing recurrent disease.

Polymorphisms of the vitamin D receptor gene predict the onset of surgical menopause in Caucasian females.

We tested association of four single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR) with age at surgical and natural menopause in a sample of Caucasians composed of 153 women with surgical and 260 with natural menopause. A significant association was observed between age at surgical menopause and two SNPs, rs1544410 (BsmI) and rs731236 (TaqI) (p < 0.05).

Accurate haplotype inference for multiple linked single-nucleotide polymorphisms using sibship data.

Sibships are commonly used in genetic dissection of complex diseases, particularly for late-onset diseases. Haplotype-based association studies have been advocated as powerful tools for fine mapping and positional cloning of complex disease genes. Existing methods for haplotype inference using data from relatives were originally developed for pedigree data.

Impacts of QTL x environment interactions on genetic response to marker-assisted selection.

Genotype x environment (GE) interaction is a common characteristic for quantitative traits, and has been a subject of great concern for breeding programs. Simulation studies were conducted to investigate the effects of GE interaction on genetic response to marker-assisted selection (MAS). In our study we demonstrated that MAS is generally more efficient than phenotypic selection in the presence of GE interaction, and this trend is more pronounced for developing broadly adaptable varieties.

Tests of linkage and association of PTH/PTHrP receptor type 1 gene with bone mineral density and height in Caucasians.

Parathyroid hormone/parathyroid hormone-related peptide receptor type 1 (PTHR1) plays an important role in calcium metabolism. It was previously shown to influence variation in bone mineral density (BMD). To investigate its importance in a typical U.

Mapping quantitative trait loci for cross-sectional geometry at the femoral neck.

Unlabelled: A genome-wide linkage scan was performed in a sample of 79 multiplex pedigrees to identify genomic regions linked to femoral neck cross-sectional geometry. Potential quantitative trait loci were detected at several genomic regions, such as 10q26, 20p12-q12, and chromosome X.

Introduction: Bone geometry is an important determinant of bone strength and osteoporotic fractures.

Predictive factors for age at menopause in Caucasian females.

Objective: Early onset of menopause results in the premature exposure to low estrogen levels and is associated with a number of postmenopausal health problems and higher risk of mortality. The aim of this study was to determine genetic and environmental factors associated with age at natural and surgical menopause.

Methods: Multiple regression analysis using a sample of Caucasians composed of 154 females with surgical and 248 with natural menopause.

Improvement of mapping accuracy by unifying linkage and association analysis.

It is well known that pedigree/family data record information on the coexistence in founder haplotypes of alleles at nearby loci and the cotransmission from parent to offspring that reveal different, but complementary, profiles of the genetic architecture. Either conventional linkage analysis that assumes linkage equilibrium or family-based association tests (FBATs) capture only partial information, leading to inefficiency. For example, FBATs will fail to detect even very tight linkage in the case where no allelic association exists, while a violation of the assumption of linkage equilibrium will result in biased estimation and reduced efficiency in linkage mapping.

Race and sex differences and contribution of height: a study on bone size in healthy Caucasians and Chinese.

Osteoporosis is characterized by a loss of bone strength, of which bone size (BS) is an important determinant. However, studies on the factors determining BS are relatively few. The present study evaluated the independent effects of height, age, weight, sex, and race on areal BS at the hip and spine, measured by dual-energy X-ray absorptiometry, while focusing on the differential contributions of height to BS across sex, race, and skeletal site.

Contribution of genotype and ethnicity to bone mineral density variation in Caucasians and Chinese: a test for five candidate genes for bone mass.

Background: Ethnicity is shown to be one of important factors affecting bone mineral density (BMD). The present study was performed to compare the association of six markers for five candidate genes with BMD variation in two populations of different ethnicity, Caucasian and Chinese, and the contribution of genotype and ethnicity to this variation in the populations.

Methods: The studied restriction fragment length polymorphisms were BsaH I of the calcium-sensing receptor gene, SacI of the alpha2HS-glycoprotein (AHSG) gene, PvuII and XbaI of the oestrogen receptor alpha gene, ApaI of the vitamin D receptor (VDR) gene and BstBI of the parathyroid hormone gene.

Association tests of interleukin-6 (IL-6) and type II tumor necrosis factor receptor (TNFR2) genes with bone mineral density in Caucasians using a re-sampling approach.

Interleukin 6 (IL-6) and tumor necrosis factor (TNF) are important cytokines for bone turnover. In this study, a promoter C-174G single-nucleotide polymorphism (SNP) within the IL-6 gene affecting the transcription rate of IL-6 and an exon 6 T676G SNP of the TNF receptor 2 (TNFR2) gene causing an M196R amino-acid change were examined for their relationship with bone mineral density (BMD). Four hundred and five multi-offspring Caucasian families, including 389 male children and 744 female children, were used.

Hotelling's T2 multivariate profiling for detecting differential expression in microarrays.

The most widely used statistical methods for finding differentially expressed genes (DEGs) are essentially univariate. In this study, we present a new T(2) statistic for analyzing microarray data. We implemented our method using a multiple forward search (MFS) algorithm that is designed for selecting a subset of feature vectors in high-dimensional microarray datasets.

Linkage and association analyses of the UCP3 gene with obesity phenotypes in Caucasian families.

Uncoupling protein 3 (UCP3) uncouples ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting the efficiency of energy metabolism. Genetic variations in the UCP3 gene have been conceived to affect body weight in the general population. In this study, using the quantitative transmission disequilibrium test (QTDT), we assessed linkage and association between the UCP3 gene and obesity phenotypes in a large sample of 1,873 subjects from 405 United States Caucasian nuclear families.

Lack of evidence for a major gene in the Mendelian transmission of BMI in Chinese.

Objectives: To determine the heritability of BMI and to examine the mode of inheritance of BMI variation in Chinese.

Research Methods And Procedures: Familial correlation and complex segregation analyses for BMI were undertaken in a Chinese sample composed of 392 nuclear families, with 1190 total individuals.

Results: A moderate heritability was found for BMI (h2 = 0.