Journal of Genetics最新文献

Pediatric cardiomyopathies (CM) are rare and challenging to diagnose due to the complex and mixed phenotypes. With the advent of next-generation sequencing (NGS), variants in several genes associated with CM have been identified, such as Troponin C (TnC), encoded by the TNNC1 gene. De novo variants in TNNC1 have been associated with different types of CM, including dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The American College of Medical Genetics and Genomics recently added TNNC1 to their recommended list of genes for reporting secondary findings. In this study, we report a de novo variant, c.100G>C (p.Gly34Arg) in the TNNC1 gene identified in three siblings with a diagnosis of severe DCM causing infant death for one of the siblings and stillbirth in the other two pregnancies. The identification of the same de novo variant in all affected siblings is suggestive of germline mosaicism in this family.

Volunteer wheat is a kind of wheat with weed characteristics, distributed widely in the main wheat-producing areas of China. It seriously damages the yield and quality of cultivated wheat. To study the genetic diversity and population structure within and between volunteer wheat and cultivated wheat (Triticum aestivum L.), 195 volunteer wheat seeds and 29 cultivated wheat seeds were analysed based on 16 pairs of highly-polymorphic microsatellite simple sequence repeats (SSR) primers and a microchip capillary electrophoresis (MCE) detection system. A total of 110 polymorphic alleles were detected by MCE with each pair of primers identifying 2-15 alleles with an average of 6.875 alleles. The polymorphic information content (PIC) ranged from 0.1089 to 0.7843, with an average of 0.5613. Genetic diversity arguments from 224 samples showed that the volunteer wheat was more varied than cultivated wheat. Based on the SSR information, the 224 samples were classified into seven groups, which corresponded to the volunteer wheats and cultivated wheats through principal coordinates analysis (PCA). We propose that the volunteer wheat and cultivated wheat have rather distant phylogenetic relationships. Hence, it is important for wheat breeding to study the genetic relationship between volunteer wheat and cultivated wheat.

Leptin is an adipocyte-secreted hormone which is involved in the regulation of food intake and energy expenditure. To ascertain the potential association between leptin gene (LEP) -2548G>A and 19A>G polymorphisms and obesity risk in the north Indian Punjabi population, a group of 250 obese and 300 control subjects were randomly selected. Both the polymorphisms in the LEP gene -2548G>A (GG vs AA: odds ratio (OR), 1.44; 95% confidence interval (CI), 0.87-2.38) and 19 A>G (AA vs GG: OR, 2.31; 95% CI, 1.32-4.05) were significantly associated with an increased risk of obesity. Logistic regression analysis revealed the significant associations in a recessive genetic model (OR=2.061; 95% CI: 1.14-3.73) and (OR= 2.57; 95% CI: 1.43-4.63) respectively for -2548G>A and 19A>G polymorphisms after adjusting for various covariates of obesity, thus, confirming the major role of anthropometric and environmental factors in this population. Haplotype analysis identified that G-G haplotype conferred approximately two-fold increased obesity risk (P=0.002). The -2548A allele and the selected obesity related covariates accounted for 53%, 26% and 30.2% variability in body mass index (BMI), waist-to-hip ratio (WHR) and triglycerides (TG), respectively. Similarly, the 19G allele contributed 75%, 27% and 36% of the variability in the waist circumference (W-crc), and WHR and TG levels, respectively in the obese individuals. Therefore the present study has revealed that both LEP -2548G>A and 19A>G polymorphisms have an important role in a individual's susceptibility towards obesity and thus could serve as relevant obesity markers in the north Indian Punjabi population.

Schizophrenia (SZ) is a highly inherited disease that affects ~0.5% of the population. The genetic and environmental factors are involved in its aetiology and they interact with each other. Combination of symptoms is unique to each patient, the disease seriously interferes with the ability to function in society and affects the mental state of the patient. In most patients, the first manifestations of SZ appear during the adolescence or early adulthood. The hypothesis that SZ origin in impaired development of the nervous system is currently widely accepted. Some studies have identified several genetic and environmental factors that increase the risk of the disease manifestation, but none of them can be considered as the only cause of SZ. The genetics of the disease is complex and in last two decades it is assumed that the cryptic rearrangements could be one of its causes. Cryptic rearrangements (microdeletions and microduplications) are the chromosomal rearrangements smaller than 3-5 Mb. Their discovery was conditioned by the development of molecular genetic and molecular cytogenetic techniques. The aberrations affect one or more genes and change the gene dose. In this article, we present the rearrangements of the regions of human chromosomes more closely associated with the onset and development of SZ. Next, the candidate genes will be presented together with their inclusion in the context of theories trying to explain the origin of SZ through some important factors (e.g. action of dopamine or glutamate or GABA, formation of dendrites and neuronal synapses, etc.).

The ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms have been shown to be associated with various human diseases and pathological conditions such as cardiovascular disease and Alzheimer's disease. However, these associations remain unclear and inconclusive. Interestingly, short telomere length was also observed in these diseases. In the present study, our aims were to investigate the interaction between two selected ABCA1 polymorphisms (-565C/T and R219K) and telomere length in a Chinese rural population including 1629 subjects and explore the underlying mechanisms. Genotyping was conducted using Taqman SNP Genotyping Assays. Mean relative leukocyte telomere length was measured using monochrome multiplex quantitative PCR method. We found that the telomere length of R219K RR genotype was significantly shorter than RK or KK genotypes (1.242 ± 0.198 vs 1.271 ± 0.207, P = 0.027 and 1.242 ± 0.198 vs 1.276 ± 0.209, P = 0.021, respectively). While the neutrophil to lymphocyte ratio (NLR) of R219K RR genotype was significantly higher than KK genotype (1.929 ± 0.826 vs 1.768 ± 0.893, P = 0.019). In the general linear models after adjustments for confounding factors, the KK and RK genotypes were both significantly associated with telomere length and NLR. A significant association was also observed for K allele carrier genotypes when compared with RR genotype for telomere length and NLR. In conclusion, the R219K polymorphism of ABCA1 was independently associated with telomere length. R219K K allele could be protective against shortening of telomeres and inflammation.

The objective of the study was to perform the prenatal diagnosis of two foetuses with 22q11.2 duplication for 2.5 Mb after noninvasive prenatal testing (NIPT), and to explore the prenatal diagnosis and genetic characteristics of these foetuses. After amniocentesis, each foetus was diagnosed through karyotype analysis and single-nucleotide polymorphism array (SNP-array), and copy number variation using shotgun sequencing (CNV-seq) was carried out on each mother's peripheral blood for comparative analysis. Both pregnant woman 1 and pregnant woman 2 had foetal amniotic fluid chromosomal karyotypes of 46, XN. The SNP-array result for foetus 1 was arr[hg19] 22q11.21(18,648,856-21,800,471) x3; namely, 22q11.2 had a 3.1 Mb repeat, and the SNP-array result of foetus 2 was arr[hg19]22q11.2(18,648,855-21,464,764) x3; there was a 2.4 Mb repeat of 22q11.2. The CNV-Seq result of the peripheral blood of pregnant woman 1 was seq[hg19]22q11.2(18,953,139-21,449,967) x3; namely, in this mother's 22q11.2 region, there was ~2.5 Mb of duplicate fragment that was pathogenic to CNV. We confirmed that case 1 was inherited from the mother by CNV-seq. In both cases, however, there were key region deletions, including 41 OMIM genes such as CLTCL1, HIRA and TBX1. Both SNP-array and CNV-seq can effectively diagnose 22q11.2 duplication syndrome and clarify its fracture site and involved genes, which may facilitate understanding of the genotype and phenotype correlations.

Crohn's disease (CD) is a chronic idiopathic inflammatory bowel condition that can affect any part of the gastrointestinal tract. Several hundred candidate loci or genes including PTPN2 have been reportedly associated with CD. A whole-exome sequencing (WES) was conducted in a 9-year-old Lebanese girl with a CD onset at 13 months and in both her asymptomatic parents. The analysis detected an extremely rare homozygous variant in PTPN2: c.359C>T, p.(Ser120Leu) in the patient, while both her parents were heterozygous. This variant, located in the protein tyrosine phosphatase (PTP) domain within a highly conserved amino acid, is classified as VUS according to the American College of Medical Genetics (ACMG) criteria. To evaluate the hypothetical functional consequences of the identified variant, a quantitative expression analysis of PTPN2 was performed in blood tissues of the patient, her parents, and two healthy controls. PTPN2 expression was not noted in the patient compared to her parents and the normal controls, suggesting a functional PTPN2 impairment caused by c.359C>T. This variant c.359C>T, p.(Ser120Leu) in PTPN2 has never been previously described in the literature. Our report suggests an association of PTPN2: c.359C>T with early-onset CD.

Vanishing of white matter (VWM) is a hereditary heterogeneous brain disorder that most often affects children. However, the onset of the disease varies from childhood to adulthood. VWM is caused by mutations in one of the five genes encoding subunits of the eukaryotic initiation factor eIF2B. In the current study, we aimed to determine the genetic cause of VWM in a large consanguineous Iranian family with three affected members. Next-generation sequencing was conducted on the proband to determine the underlying cause of VWM. The identified variant was validated by PCR-Sanger sequencing in the patient and was also segregated in his parents and two other affected members of the pedigree. The potential functional effects of this mutation within EIF2B5 were predicted by in silico analysis. We have also reviewed all EIF2B5 disease-causing variants and available clinical features of each patient reported in HGMD Professional 2022.2. A novel homozygous variant c.746T>G [p.Ile249Ser] was detected in EIF2B5 which was co-segregated with the disease in all affected family members in an autosomal recessive manner. All employed in silico prediction tools and 3D structure analysis for the novel mutation also supported the pathogenicity of this variant. Our study not only expanded the spectrum of the pathogenic variants in EIF2B5 but also presented a literature review on EIF2B5-related conditions that provide a comprehensive picture of the genetic nature of this gene and phenotypic variability in patients.

Mastitis is a serious bovine disease which causes significant commercial loss. Polymorphism of mannose-binding lectin genes in bovine may be regarded as a functional and positional candidate gene for mastitis resistance and complement activity. In the present study, single-nucleotide polymorphism (SNP) of MBL2 gene in 200 Murrah buffaloes was investigated using the polymerase chain reaction direct sequence (PCR direct sequence) technique, and four new SNPs at 1262G>A, 3382A>T, 4387C>T and 4511C>T loci of Mannose binding lectin 2 (MBL2) gene were found. Pair linkage disequilibrium analysis and haplotype construction of MBL2 gene were performed using SHEsis software. Two nonsynonymous types of changes were observed at 1262G>A (Gly40Asp) and 4387C>T (Thr166Met) of MBL2 protein. These amino acid changes were however predicted not to affect the protein function in any manner. An odds ratio analysis showed that the A allele of 1262G>A, A allele of 3382A>T, C allele of 4387C>T and C allele of 4511C>T had 3.7, 5.19, 7.82 and 3.7 fold increased risk for developing clinical mastitis in Murrah buffaloes, respectively, identifying that these alleles are 'at-risk' alleles and showed significant association with increased risk for clinical mastitis in Murrah buffaloes (P<0.01). Genotypic association analysis revealed that Murrah buffaloes with AG, AT, CT and TT genotypes at 1262G>A, 3382A>T, 4387C>T and 4511C>T loci of ,MBL2 gene, respectively were found significantly least susceptible to clinical mastitis compared to other genotypes. A total of seven haplotypes were constructed from four SNPs of MBL2 gene. Haplotypes association analysis showed that animals with allelic combination of haplotypes Hap6 (GTCT) and Hap7 (GTTT) were significantly least susceptible to clinical mastitis compared to other haplotypes in Murrah buffaloes (P<0.01).