Mitochondrial genomes of Anisakis simplex and Contracaecum osculatum (sensu stricto) – Comparisons with selected nematodes

Anisakid nematodes parasitize mainly fish, marine mammals and/or fish-eating birds, and can be transmitted to a range of fish-eating mammals, including humans, where they can cause gastrointestinal disease linked to larval infection or allergic responses. In spite of the animal and human health significance of these parasites, there are still gaps in our understanding of the systematics, biology, epidemiology and ecology of anisakids. Mitochondrial (mt) DNA provides useful genetic markers for investigations in these areas, but complete mt genomic data have been lacking for most anisakids. In the present study, the mt genomes of Anisakis simplex sensu stricto and Contracaecum osculatum sensu stricto were amplified from genomic DNA by long-range polymerase chain reaction and sequenced using 454 technology. The circular mt genomes of these species were 13,926 and 13,823 bp, respectively, and each of them contained 12 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes consistent for members of the Ascaridida, Oxyurida, Spirurida, Rhabditida and Strongylida. These mt genomes provide a stepping-stone for future comparative analyses of a range of anisakids and a basis for reinvestigating their genetic relationships. In addition, these markers might be used in prospecting for cryptic species and exploring host affiliations.     

In vitro responses to known in vivo genotoxic agents in mouse germ cells

Genotoxic compounds have induced DNA damage in male germ cells and have been associated with adverse clinical outcomes including enhanced risks for maternal, paternal and offspring health. DNA strand breaks represent a great threat to the genomic integrity of germ cells. Such integrity is essential to maintain spermatogenesis and prevent reproduction failure. The Comet assay results revealed that the incubation of isolated germ cells with n‐ethyl‐n‐nitrosourea (ENU), 6‐mercaptopurine (6‐MP) and methyl methanesulphonate (MMS) led to increase in length of Olive tail moment and % tail DNA when compared with the untreated control cells and these effects were concentration‐dependent. All compounds were significantly genotoxic in cultured germ cells. Exposure of isolated germ cells to ENU produced the highest concentration‐related increase in both DNA damage and gene expression changes in spermatogonia. Spermatocytes were most sensitive to 6‐MP, with DNA damage and gene expression changes while spermatids were particularly susceptible to MMS. Real‐time PCR results showed that the mRNA level expression of p53 increased and bcl‐2 decreased significantly with the increasing ENU, 6‐MP and MMS concentrations in spermatogonia, spermatocytes and spermatids respectively for 24 hr. Both are gene targets for DNA damage response and apoptosis. These observations may help explain the cell alterations caused by ENU, 6‐MP and MMS in spermatogonia, spermatocytes and spermatids. Taken together, ENU, 6‐MP and MMS induced DNA damage and decreased apoptosis associated gene expression in the germ cells in vitro. Environ. Mol. Mutagen. 58:99–107, 2017. © 2017 Wiley Periodicals, Inc.     

Molecular genetics of congenital nuclear cataract

A cataract is defined as opacification of the normally transparent crystalline lens. Congenital cataract (CC) is a type of cataract that presents at birth or during early childhood. CC is one of the most common causes of visual impairment or blindness in children worldwide. Approximately 50% of all CC cases may have a genetic cause which is quite heterogeneous. CC occurs in a variety of morphologic configurations, including polar/subcapsular, nuclear, lamellar, sutural, cortical, membranous/capsular and complete. Nuclear cataract refers to the opacification limited to the embryonic and/or fetal nuclei of the lens. Although congenital nuclear cataract can be caused by multiple factors, genetic mutation remains to be the most common cause. It can be inherited in one of the three patterns: autosomal dominant, autosomal recessive, or X-linked transmission. Autosomal dominant inheritance is the most frequent mode with high penetrance. There may be no obvious correlation between the genotype and phenotype of congenital nuclear cataract. Animal models have been established to study the pathogenesis of congenital nuclear cataract and to identify candidate genes. In this review, we highlight identified genetic mutations that account for congenital nuclear cataract. Our review may be helpful for genetic counseling and prenatal diagnosis.     

Tryptophan hydroxylase type 2 variants modulate severity and outcome of addictive behaviors in Parkinson's disease

BackgroundImpulse control disorders and compulsive medication intake may occur in a minority of patients with Parkinson's disease (PD). We hypothesize that genetic polymorphisms associated with addiction in the general population may increase the risk for addictive behaviors also in PD.MethodsSixteen polymorphisms in candidate genes belonging to five neurotransmitter systems (dopaminergic, catecholaminergic, serotonergic, glutamatergic, opioidergic) and the BDNF were screened in 154 PD patients with addictive behaviors and 288 PD control subjects. Multivariate analysis investigated clinical and genetic predictors of outcome (remission vs. persistence/relapse) after 1 year and at the last follow-up (5.1 ± 2.5 years).ResultsAddictive behaviors were associated with tryptophan hydroxylase type 2 (TPH2) and dopamine transporter gene variants. A subsequent analysis within the group of cases showed a robust association between TPH2 genotype and the severity of addictive behaviors, which survived Bonferroni correction for multiple testing. At multivariate analysis, TPH2 genotype resulted the strongest predictor of no remission at the last follow-up (OR[95%CI], 7.4[3.27–16.78] and 13.2[3.89–44.98] in heterozygous and homozygous carriers, respectively, p < 0.001). The extent of medication dose reduction was not a predictor. TPH2 haplotype analysis confirmed the association with more severe symptoms and lower remission rates in the short- and the long-term (p < 0.005 for all analyses).ConclusionThe serotonergic system is likely to be involved in the pathophysiology of addictive behaviors in PD, modulating the severity of symptoms and the rate of remission at follow-up. If confirmed in larger independent cohorts, TPH2 genotype may become a useful biomarker for the identification of at-risk individuals.     

Primary Aldosteronism: A New Understanding

Primary aldosteronism (PAL) may always have a genetic basis. This leads to either abnormally regulated, increased biosynthesis (Familial Hyperaldosteronism Type I, FHI) or to unrestrained hyperplasia and neoplasia, usually benign. The distinction between diffuse hyperplasia, nodular hyperplasia and adenoma may be relatively unimportant in functional and etiological terms. The genetic basis must be understood before diagnosis of disease (FHI) or of predispostion (all other PAL) can be made at birth and appropriate surveillance commenced. The natural history of PAL other than FHI is for a progressive increase in severity, with both adrenals eventually involved. Long-term follow-up of PAL is therefore mandatory, and postoperative assessment of residual non-suppressible aldosterone production by fludrocortisone suppression testing useful in defining biochemical cure or improvement, and the need for specific medical treatment.     

Familial Resemblance of Blood Pressure and Body Weight

Familial resemblance of blood pressure (BP) was studied in 545 families of which 370 included natural children, 24 adopted children and 151 both natural and adopted children. Mean values of four automatic BP measurements (Dinamap 845) were converted into age (adult) or height (children) and sex adjusted scores. BP was compared between parents and randomly chosen index children. A significant resemblance of BP was observed between natural children and their parents: r = 0.24 for systolic BP, r = 0.29 for diastolic BP, (n = 272 p > 0.05). BP of adopted children did not resemble that of their foster parents except for a significant correlation to BP of the adopting mothers (n = 46). Weight, heart rate, age and time of common life shared did not influence the results. The relative contribution of genetic and common environmental factors to BP correlation between family members could not be evaluated in this study. BP of children whose parents have high BP should be monitored regularly.     

Associations Among GABRG1, Level of Response to Alcohol, and Drinking Behaviors

Background:  Recent studies of the genetics of alcoholism have focused on a cluster of genes encoding for γ-aminobutyric acid (GABA_A) receptor subunits, which is thought to play a role in the expression of addiction phenotypes. This study examined allelic associations between 2 single nucleotide polymorphisms (SNPs) of the GABRG1 gene (rs1391166 and rs1497571) and alcohol phenotypes, namely level of response to alcohol, alcohol use patterns, and alcohol-related problems.
Method:  Participants were non-treatment-seeking seeking hazardous drinkers ( n  = 124) who provided DNA samples, participated in a face-to-face interview for level of response to alcohol, and completed a series of drinking and individual differences measures.
Results:  Analyses revealed that a SNP of the GABRG1 gene (rs1497571) was associated with level of response to alcohol and drinking patterns in this subclinical sample. Follow-up mediational analyses were also conducted to examine putative mechanisms underlying these associations.
Discussion:  These findings replicate and extend recent research suggesting that genetic variation at the GABRG1 locus may underlie the expression of alcohol phenotypes, including level of response to alcohol.     

同型半胱氨酸及其相关酶基因多态性与糖尿病周围神经病变的关系

研究对象为 2型糖尿病 (DM )有周围神经病变组 (60例 )、2型DM无周围神经病变组 (4 6例 )和正常对照组 (5 0例 )。分别测定 3组血浆同型半胱氨酸 (Hcy) ,血清叶酸、维生素B12 水平及Hcy代谢关键酶亚甲基四氢叶酸还原酶 (MTHFR)的基因型。结果显示 ,高Hcy及低叶酸、维生素B12 水平与 2型DM患者伴发周围神经病变相关 ,而MTHFR的基因多态性只与DM有关而与DM周围神经病变无相关性。