Journal of Genetics最新文献

We report the case of a Spanish pediatric patient with developmental delay, hypotonia, feeding difficulties, visual problems, and hyperkinetic movements. Whole-exome sequencing uncovered a new heterozygous de novo Synaptotagmin 1 (SYT1) missense variant, NM_005639.3:c.930T>A (p.Asp310Glu), in a female proband. This gene encodes the synaptotagmin-1 (SYT1) protein, which is a component of a protein complex involved in the fusion of synaptic vesicles with the presynaptic membrane. Pathogenic SYT1 variants have been associated with Baker–Gordon syndrome (BAGOS), an autosomal dominant neurodevelopmental disorder. Although up to 30 cases have been identified worldwide, to the best of our knowledge, this is the first patient described with mitochondrial respiratory chain deficiencies and rod–cone dysfunction. In conclusion, our data expand both the genetic and phenotypic spectrum associated with SYT1 variants.

Colorectal cancer (CRC) is known to develop due to the accumulation of both genetic and epigenetic alterations, resulting in the conversion of intestinal epithelial cells to malignant adenocarcinoma cells. Caudal type homeobox 1 (CDX1) gene is a homeobox transcription factor and a selective tumour suppressor gene that is an important factor for the development of intestinal cells. This gene plays a role in the differentiation of intestinal epithelial cells, and its expression decreases in a number of cell lines derived from CRC, which suggests that a lack of CDX1 expression is a risk factor for the development of colorectal carcinoma. Therefore, the methylated DNA amounts of CDX1 gene in stool samples were investigated as a noninvasive method for the detection of CRC. In the present study, the methylation of CDX1 gene promoter region was assessed in stool samples of 50 CRC patients and 50 healthy individuals by MethyLight PCR using two primers and a Taq Man probe, which was completely specifically designed for fully methylated DNA of the gene promoter region. The percentage of methylated reference (PMR) of the studied gene in all samples was calculated similarly to previous studies. Statistical analysis was performed using SPSS 16. The PMR medians were 3.25 (95% CI: 0.1–100) and 0.1 (95% CI: 0.07–1) in the stool samples of CRC patients and healthy individuals, respectively. The results showed a significant difference in CDX1 gene PMR between stool samples of CRC patients and controls (P-value <0.001). According to the results of this study, it can be argued that measurement of CDX1 gene DNA in stool samples using the MethyLight PCR has acceptable sensitivity and specificity, and is adequately potential to be used as a noninvasive complementary method for the diagnosis of CRC, along with colonoscopy as the gold standard to this end. This study is the first report on CDX1 methylation in stool samples of CRC patients. Therefore, further research should be carried out with a larger sample size to evaluate its efficacy as a diagnostic biomarker in clinical laboratories.

Trachoma, caused by Chlamydia trachomatis, is the most common infectious blindness in the world and is present in indigenous Mayan from Chiapas (Mexico). Inflammatory genes are activated when suffering from trachoma, thus some polymorphisms could increase the susceptibility to develop irreversible blindness. This study aimed to evaluate the genetic risk of developing late-stage trachoma in Mayan ethnic groups. In a case–control study (n = 51 vs n = 102, respectively), the following single-nucleotide polymorphisms (SNPs) in genes related to inflammation were analysed: HSD11B1 (rs11807619), HSD11B1 (rs932335), ABCG2 (rs2231142), SLCO1B1 (rs4149056), IL-10 (rs1800890), TNF (rs1800629), MMP2 (rs243865) and ACE. Three SNPs were associated with late-stage trachoma risk: (i) the T allele of rs11807619, (ii) the C allele of rs932335, which are linked to the HSD11B1 gene (OR = 22.5–27.3), particularly in men when adjusts for gender (OR = 16–16.7); and (iii) D allele of rs4340 in the ACE gene (OR = 5.2–5.3). In fact, significant linkage disequilibrium demonstrated association between ACE gene and HSD11B1 SNPs (r = 0.17–0.179; P = 0.0048–0.0073). Two SNPs HSD11B1 gene (P = 0.013 vs 0.0039) and HSD11B1–ACE haplotypes showed association with late-stage trachoma in Mayan ethnic groups.

In the past, there were no easily distinct and recognizable features as a guide for precise clinical and genetic diagnosis of cases with chromosome microdeletions involving 15q26 including CHD2. The present study analysed the clinical data and collected venous blood samples from a pediatric patient and his healthy family members for DNA testing. The whole-exome sequencing was performed by the next-generation sequencing (NGS). Chromosomal copy-number variations were tested based on NGS. We present a review of all cases with chromosome microdeletions affecting CHD2. A novel de novo 5.82-Mb deletion at 15q25.3-15q26.1 including CHD2 was identified in our patient who is an 11.6-year-old boy. We first found surprising efficacy of lamotrigine in controlling intractable drop seizures in the individual. These cases have development delay, behavioural problems, epilepsy, variable multiple anomalies, etc. Phenotypes of individuals with deletions involving 15q26 including CHD2 are highly variable with regard to facial features and multiple developmental anomalies. We first found the special clinical entity of development delay, behavioural problems, epilepsy, variable skeletal and muscular anomalies, abnormalities of variable multiple systems and characteristic craniofacial phenotypes in patients with chromosome microdeletions involving CHD2. The larger deletions involving 15q26 including CHD2 tend to cause the classical phenotype. A distinctive craniofacial appearance of the classical phenotype is midface hypoplasia and perifacial protrusion.

Genomic studies make it possible to breakthrough in many fields such as biochemistry, physiology, phylogenetics, etc., though they are unworkable without sequences of genomic DNA of an organism. The terrestrial mollusks’ genomes would benefit gastropod biology investigations, that are unavailable so far due to problems in DNA integrity and quality after the isolation procedures. Here we describe a fast and handy protocol for genomic DNA extraction from the tissues of Helix lucorum, which allows to yield high-quality samples applicable for downstream analysis such as high-throughput DNA sequencing. Troubleshooting revealed the nuclease activity of snail tissue lysate, which may be avoided by heating the lysate and decreasing the incubation time.

The mitogenome is an important tool for taxonomic and evolutionary investigation. Here, a few complete mitogenomes of red algae have been reported. We have reported the complete mitogenome sequences of Grateloupia cornea Okamura, 1913 (Rhodophyta, Halymeniales). The genome is 30,595 bp in circumference, and has a strongly biased [AT] = 66.9%. Like most other Grateloupia species, it has a group II intron in the cox1 gene. Maximum likelihood and maximum parsimony analyses showed that G. cornea is more closely related to G. asiatica. This shows that the group II intron in the cox1 ORF present in most species of Grateloupia was present in their common ancestor, and uniquely lost in G. asiatica. The seven Grateloupia species with known mitogenome sequences remain monophyletic, with the genus Polyopes as sister taxon. The complete mitochondrial genome data will be valuable for future research on comparative mitochondrial genome analysis, an extensive understanding of gene content and organization, evolution of the cox1 intron in Rhodophyta as well as phylogenetic analysis.

We present here the complete mitochondrial sequence of the critically endangered Malaysian giant turtle, Orlitia borneensis. The assembled mitochondrial genome includes 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA genes (rRNAs), and one control region. This mitochondrial genome has been archived in the NCBI GenBank with accession number OQ808845. The Batagur control region is relatively smaller than O. borneensis and closer to Aldabrachelys gigantea, which suggests potentially that O. borneensis has undergone an expansion in the control region.

Phenotypic mutants are valuable resources for elucidating the function of genes responsible for their expression. This study examined mutant rice strains expressing three traits: spotted leaf 6 (spl6), lax panicle (lax), and liguleless (lg). In the mutant, the spl6 phenotype was a genetically programmed lesion-mimicking mutation (LMM) that displayed spontaneously scattered spots across the leaf surface. In the lg trait, the plant lacked a collar region, and there were no auricles and ligules at the junction of the leaf blade and leaf sheath. The lax panicle trait manifested as sparely arranged spikelets resulting from the terminal spikelet with no lateral spikelets, which caused a drastic reduction of the total seed number in the mutant. All three mutant genes were genetically recessive and had nuclear gene regulation. The dihybrid segregation of the lg gene was classified independently according to the Mendelian 9:3:3:1 dihybrid segregation ratio in the F₂ generation, suggesting that the lg gene is not linked to the same chromosome as the lax and spl6 genes. On the other hand, spl6 and lax were not assorted independently, indicating that they are closely linked on chromosome 1 in rice. Additional linkage analysis from the recombination of spl6 and lax genes reconfirmed that the two genes were ~9.4 cM away from each other. The individual single-gene mutant plant from one plant with a three-gene mutation (spl6, lax, and lg) was isolated and characterized, which will be a crucial resource for the gene cloning and molecular characterization of these genes.

In acute lymphoblastic leukaemia (ALL), elevated foetal haemoglobin (HbF) levels have been associated with the prognosis of patients. Genetic variants in HbF regulatory genes: BAF chromatin remodelling complex subunit (BCL11A), HBS1L-MYB transcriptional GTPase intergenic region (HBS1L-MYB), Krüppel-like factor 1 (KLF1), haemoglobin gamma subunit 2 (HBG2), haemoglobin gamma subunit 1 (HBG1), and haemoglobin subunit beta pseudogene 1 (HBBP1) are often associated with elevated HbF concentration. This study investigated the association of genetic variants in HbF regulatory genes with HbF concentration, unfavourable prognosis, and outcome in children with ALL. We quantified HbF concentration and genotyped 17 genetic variants in 48 patients with ALL and 64 children without ALL as a reference group. HbF concentration was higher in patients than in the reference group (4.4% vs 1.4%), and 75% (n = 36) of the patients had HbF > 2.5%. Unfavourable prognosis ALL was established in 68.8% (n = 33) of the patients. Variant HBG2 rs7482144 was associated with high HbF concentration (P = 0.015); while HBS1L-MYB rs9399137 (P = 0.001), HBG2 rs7482144 (P = 0.001) and the β-globin genes HBG2, HBG1, and HBPP1 haplotype TGC (P = 0.017) with unfavourable prognosis ALL. Additionally, variant BCL11A rs4671393 showed a protective role (P = 0.0001). In conclusion, variants HBG2 rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 may play a significant role in ALL.

A recent report by G. Clark points to a sustained persistence of social status in England that extends vertically across several generations and horizontally across many levels of kinship. We seek to put his findings in historical perspective. We do so by relating them to two lines of thinking related to biological inheritance. One predated the rediscovery of Mendel’s work and led to the field of quantitative genetics, which dealt on the whole with quasi-continuously varying traits. The other is based on the rediscovery itself and led to a reconciliation between quantitative genetics and discrete Mendelian elements of heredity. Both were enmeshed with the supposed need for, and societal consequences of, eugenics and assortative mating. Also on both issues, the significant ideas can be traced to R. A. Fisher, inspired in one case by F. Galton and in the other by J. A. Cobb, with strong support for Galton and Cobb coming from Karl Pearson. Clark’s findings point to societal stratification, and assortative mating for wealth is a straightforward hypothesis to account for it. However, it should be noted that the findings support, but do not prove, the hypothesis.