Mitochondrial diversity of Yoruba and Fulani chickens: A biodiversity reservoir in Nigeria.

Poultry are the most widely distributed type of livestock in Nigeria. Indigenous chickens are extremely common throughout the country. Indeed, approximately 83 million chickens are raised in extensive systems and 60 million in semi-intensive systems. To provide the first comprehensive overview of the maternal lineages in Southwest Nigeria, we analyzed 96 mitochondrial DNA control region sequences from 2 indigenous chicken ecotypes: Fulani and Yoruba. All samples belonged to the most frequent haplogroup (E) in Africa and Europe and showed noticeably low haplotype diversity. Although only 11 different haplotypes were detected, with 2 of them never found before in Nigeria, the presence of unique sequences among our indigenous samples testified to their status as an important genetic resource to be preserved. Furthermore, a total of 7,868 published sequences were included in the comparative analysis, which revealed an east-west geographic pattern of haplogroup distribution and led to the conclusion that the gene flow from Southeastern Asia mainly involved one mitochondrial clade. Moreover, owing to the extensive genetic intermixing among Nigerian chickens, conservation efforts are required to safeguard the extant mitochondrial variability in these indigenous ecotypes and establish future improvement and selection programs.

Founder effects of the homogentisate 1,2-dioxygenase (HGD) gene in a gypsy population and mutation spectrum in the gene among alkaptonuria patients from India.

INTRODUCTION: Alkaptonuria (AKU) is a rare metabolic disease. The global incidence is 1:100,000 to 1:250,000. However, identification of a founder mutation in a gypsy population from India prompted us to study the prevalence of AKU in this population and to do molecular typing in referred cases of AKU from the rest of India. OBJECTIVE: To determine the prevalence of AKU in the gypsy population predominantly residing in the seven districts of Tamil Nadu. To determine the molecular characteristic of AKU cases referred to our clinic from various parts of India. METHOD: Urine spot test to detect homogentisic acid followed by quantitative estimation using high-performance liquid chromatography in 499 participants from the gypsy population and confirming the founder mutation in those with high levels by sequencing. Sequence the homogentisate 1,2-dioxygenase (HGD) gene to identify mutations and variants in 29 AKU non-gypsy cases. RESULTS: The founder mutation was detected in homozygous state in 41/499 AKU-affected individuals of the gypsy community giving a high prevalence of 8.4%. Low back pain, knee pain, and eye and ear pigmentation were the most common symptoms and signs respectively. The commonest mutation identified in the non-gypsy AKU cases was p.Ala122Val. CONCLUSION: High prevalence of AKU in the inbred gypsy population at 8.4% was detected confirming the founder effect. Urine screening provided a cost-effective method to detect the disease early. Mutation spectrum is varied in the rest of the Indian population. This study identified maximum number of mutations in exon 6 of the HGD gene. Key Points • High prevalence (8.4%) of alkaptonuria (AKU) in the gypsy population due to founder mutation in the HGD gene. • Inbreeding exemplifies the founder effects of this rare genetic disorder. • Urinary screening is a cost-effective method in this community for early detection of AKU and intervention. • The mutation spectrum causing AKU is diverse in the rest of the Indian population.

Peopling of India: Ancient DNA perspectives.

To reconstruct and explain patterns of genetic diversity of modern humans, understanding their past and present genetic profile is crucial. While genomes of contemporary people can provide information about present day population structure, analysis of ancient genomes may provide unprecedented insights about the past demographic events that have shaped the contemporary gene pool. Population genetics has recently witnessed an explosion in studies on ancient human population histories, primarily from Europe and America. South Asia has no representation in the ancient genomics literature, despite the wealth of archaeological richness in the form of human skeletal remains that exist in collections all over the country. Representing one-fifth of present day humanity calls for understanding the demographic history of south Asia not merely as a prerequisite but as an urgent need to understand its genetic variations on a global scale. Although the overall picture is taking form, new archaeological and genetic information from the region has started to reveal a more complex scenario of ancient human migrations and admixtures than was ever known before. In this article, we discuss a meaningful insight on the current status of ancient DNA (aDNA) research in India. We have also summarized a few but important aDNA studies, which have been successfully carried out in India. Furthermore, we have highlighted the potential opportunity of aDNA research in the Indian subcontinent.

Mitochondria in health and disease.

Mitochondrial biology has become an area of intense research owing to the unique physiology of the organelle and its role in several types of cancers and other disorders. It has been found that mitochondria-encoded proteins, mitochondrial DNA and even RNA influence the functioning of the cell in more ways than were previously imagined. This may contribute to disease phenotypes which require detailed investigation and communication to the community health care providers. Additionally, this provides several novel avenues in drug designing against various cancers, neurodegenerative diseases and other metabolic disorders. The sixth annual conference of the Society for Mitochondrial Research and Medicine - India (SMRM) titled, 'Mitochondria in Health and Disease' was organized by Rana P. Singh at the School of Life Sciences, Jawaharlal Nehru University in New Delhi, India from 10th to 11th February 2017. The underlying objective of the conference was to provide a platform to discuss the recent advances in basic and translational research in mitochondrial biology and diseases. The conference aimed to translate academic research into clinical practice by providing a forum for basic researchers and clinicians to share their knowledge and build collaborations towards development of advanced therapeutic in mitochondrial diseases. To facilitate the knowledge-sharing, six major themes for the scientific sessions were (1) understanding of mitochondrial biology in disease progression, (2) advances in basic and translational mitochondrial research, (3) mitochondria in evolution and development, (4) targeting mitochondria for cancer prevention and treatment, (5) mitochondria in metabolic and neurological disorders and (6) mitochondria in stem cell and regeneration biology. This report summarizes the major outcomes of the discussions at the conference.

NR5A1 mutations are not associated with male infertility in Indian men.

NR5A1 or steroidogenic factor 1 (SF1) is an autosomal gene, which encodes a protein that is a member of nuclear receptor family. NR5A1 regulates the transcription of numerous genes that are expressed in hypothalamic-pituitary-gonadal axis and adrenal cortex which in turn, coordinate the gonadal development, steroidogenesis and sex differentiation. Several mutations in NR5A1 have been reported to cause gonadal dysgenesis with adrenal insufficiency in individuals with 46,XY karyotype. However, studies in the past few years have shown that NR5A1 mutations can also contribute to primary ovarian insufficiency and impaired spermatogenesis. As there is no genetic study on NR5A1 in Indian infertile men, we have sequenced the entire coding region (exons 2-7) of NR5A1 in 502 infertile men of which, 414 were non-obstructive azoospermic and 88 severe oligozoospermic, along with 427 ethnically matched fertile controls. Interestingly, none of the mutations reported to be associated with male infertility were found in our study, except one polymorphism, rs1110061. However, it was not significantly different between infertile and fertile groups (p = .76). In addition, we have identified six intronic variants; but none of them was significantly associated with male infertility.

A novel gene THSD7A is associated with obesity.

Body mass index (BMI) is a non-invasive measurement of obesity. It is commonly used for assessing adiposity and obesity-related risk prediction. Genetic differences between ethnic groups are important factors, which contribute to the variation in phenotypic effects. India inhabited by the first out-of-Africa human population and the contemporary Indian populations are admixture of two ancestral populations; ancestral north Indians (ANI) and ancestral south Indians (ASI). Although ANI are related to Europeans, ASI are not related to any group outside Indian-subcontinent. Hence, we expect novel genetic loci associated with BMI. In association analysis, we found eight genic SNPs in extreme of distribution (P⩽3.75 × 10(-5)), of which WWOX has already been reported to be associated with obesity-related traits hence excluded from further study. Interestingly, we observed rs1526538, an intronic SNP of THSD7A; a novel gene significantly associated with obesity (P=2.88 × 10(-5), 8.922 × 10(-6) and 2.504 × 10(-9) in discovery, replication and combined stages, respectively). THSD7A is neural N-glycoprotein, which promotes angiogenesis and it is well known that angiogenesis modulates obesity, adipose metabolism and insulin sensitivity, hence our result find a correlation. This information can be used for drug target, early diagnosis of obesity and treatment.

Ionizing radiation effects on sex steroid hormone levels in serum and milt of freshwater fish Oreochromis mossambicus.

Effects of gamma rays on the sex steroid hormone levels [testosterone (T), 11-ketotestosterone (11-KT) and 17ß-estradiol (E2)] were studied in the freshwater fish Oreochromis mossambicus. Gamma radiation induced effects on hormone levels reported here for the first time in the fish. Since radionuclides released accidentally or during a nuclear disaster can contaminate inland water bodies, biomonitoring methods are required for assessing the impacts of certain dose levels of radiation that may ultimately result in ionizing radiation exposure to both humans and non-human biota. Three groups of (n=15 in each group) fishes were irradiated with a single dose of (60)Co 10Gy, 15Gy and 20Gy with a duration of .33, .50 and .66min. Significant decrease of the hormone levels was seen at higher doses of 15Gy and 20Gy. The sex steroid hormone levels in the fishes are vital for sperm production, development, differential functions related to the physiology and reproductive behavior. This study serves as biomonitoring tool to assess the ionizing radiation effects on reproductive behavior of aquatic biota.

Bilateral hypertrophic olivary nucleus degeneration on magnetic resonance imaging in children with Leigh and Leigh-like syndrome.

OBJECTIVE: Bilateral hypertrophic olivary degeneration on brain MRI has been reported in a few metabolic, genetic and neurodegenerative disorders, including mitochondrial disorders. In this report, we sought to analyse whether bilateral symmetrical inferior olivary nucleus hypertrophy is specifically associated with mitochondrial disorders in children. METHODS: This retrospective study included 125 children (mean age, 7.6 ± 5 years; male:female, 2.6:1) diagnosed with various metabolic and genetic disorders during 2005-2012. The routine MRI sequences (T1 weighted, T2 weighted and fluid-attenuated inversion-recovery sequences) were analysed for the presence of bilateral symmetrical olivary hypertrophy and central tegmental tract or dentate nuclei signal changes. The other imaging findings and the final diagnoses were noted. RESULTS: The cohort included patients with Leigh and Leigh-like syndrome (n = 25), other mitochondrial diseases (n = 25), Wilson disease (n = 40), Type 1 glutaric aciduria (n = 14), maple syrup urine disease (n = 13), giant axonal neuropathy (n = 5) and L-2 hydroxy glutaric aciduria (n = 3). Bilateral inferior olivary nucleus hypertrophy was noted in 10 patients, all of whom belonged to the Leigh and Leigh-like syndrome group. CONCLUSION: Bilateral hypertrophic olivary degeneration on MRI is relatively often, but not routinely, seen in children with Leigh and Leigh-like syndrome. Early detection of this finding by radiologists and physicians may facilitate targeted metabolic testing in these children. ADVANCES IN KNOWLEDGE: This article highlights the occurrence of bilateral hypertrophic olivary nucleus degeneration on MRI in children with Leigh and Leigh-like syndrome, compared with other metabolic disorders.

The "double panda" sign in Leigh disease.

Although the "face of the giant panda" sign on magnetic resonance imaging (MRI) is traditionally considered to be characteristic of Wilson disease, it has also been reported in other metabolic disorders. This study describes the characteristic "giant panda" sign on MRI in a child with Leigh disease. The diagnosis was based on the history of neurological regression; examination findings of oculomotor abnormalities, hypotonia, and dystonia; raised serum lactate levels; and characteristic brain stem and basal ganglia signal changes on MRI. The midbrain and pontine tegmental signal changes were consistent with the "face of the giant panda and her cub" sign. In addition to Wilson disease, metabolic disorders such as Leigh disease should also be considered in the differential diagnosis of this rare imaging finding.

Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations.

BACKGROUND: Mutation in the SURF1 is one of the most common nuclear mutations associated with Leigh syndrome and cytochrome c oxidase deficiency. This study aims to describe the phenotypic and imaging features in four patients with Leigh syndrome and novel SURF1 mutation. METHODS: The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006-2012). All the patients underwent a detailed neurological assessment, muscle biopsy, and sequencing of the complete mitochondrial genome and SURF1. RESULTS: Three patients had classical presentation of Leigh syndrome. The fourth patient had a later age of onset with ataxia as the presenting manifestation and a stable course. Hypertrichosis, facial dysmorphism and hypopigmentation were the additional phenotypic features noted. On magnetic resonance imaging all patients had brainstem and cerebellar involvement and two had basal ganglia involvement in addition. The bilateral symmetrical hypertrophic olivary degeneration in these patients was striking. The SURF1 analysis identified previously unreported mutations in all the patients. On follow-up three patients expired and one had a stable course. CONCLUSIONS: Patients with Leigh syndrome and SURF1 mutation often have skin and hair abnormalities. Bilateral symmetrical hypertrophic olivary degeneration was a consistent finding on magnetic resonance imaging in these patients.

Analysis of microsatellite polymorphisms in South Indian patients with non syndromic cleft lip and palate.

Non syndromic cleft lip and/or palate (NSCLP) is a complex congenital anomaly with varying incidence among patients of different geographical origins. Multiple contributing factors are known to trigger the cleft formation. There are several genes involved in the aetiology of NSCLP and they are different in different populations. The genetic components of clefts that underlie the susceptibility to respond to the environment still remain unclear. In this study, five microsatellite polymorphisms from five candidate genes were employed to analyze the association between these genes and NSCLP in 83 patients and 90 controls. Genotyping was performed by separating and visualizing the fluorescently-labeled polymerase chain reaction (PCR) products. The association of the five microsatellite polymorphisms with NSCLP was tested by using the CLUMP v1.9 program that uses the Monte Carlo method. The genotypic distribution is in Hardy-Weinberg equilibrium in the control group for only the MSX1 and DLX3 genes. The RARA microsatellite was significantly associated with NSCLP. Our results suggest that the RARA gene is involved in pathogenesis of cleft lip and palate in South Indians.

Association between neuropeptide Y gene polymorphisms and alcohol dependence: a case-control study in two independent populations.

BACKGROUND: Alcohol dependence is a chronic, progressive neurobiological brain disorder. Previous research reported an inverse association between ethanol drinking and cerebral neuropeptide Y (NPY) levels. There are conflicting results of studies on NPY gene polymorphisms in association with alcohol dependence in humans. METHODS: To assess the role of the NPY gene in alcohol dependence, we genotyped three polymorphisms--in a sample of 195 subjects from the Kota population (80 alcohol dependence and 115 controls) and 141 subjects from the Badaga population (80 alcohol dependence and 61 controls). Phenotype was defined based on the DSM-IV criteria. Genotyping was performed using sequencing. Association of the NPY gene with alcohol dependence was tested by using logistic regression and haplotype analyses and linkage disequilibrium. RESULTS: All three polymorphisms were found to be in the Hardy-Weinberg equilibrium in both populations. The results of our study reveal a significant association between G1258A and alcohol dependence in both the Kota and Badaga populations. The linkage disequilibrium between the markers is not strong or significant. Haplotype analysis also did not show significant association between the NPY gene and alcohol dependence. CONCLUSION: These data support the hypothesis that alcohol dependence is influenced by the NPY G1258A polymorphism in Indian populations.

Growth of N-Glycyl-L-Valine (GV) single crystal and its spectral, thermal and optical characterization.

A nonlinear optical crystal of N-Glycyl-L-Valine (GV) single crystals was grown by slow evaporation solution growth technique from an aqueous solution. The unit cell parameters and the crystal structure were determined by single crystal X-ray diffraction study. The Fourier transform infrared (FTIR) and proton nuclear magnetic resonance ((1)H NMR) spectral studies were carried out to identify the functional groups of the grown crystals. The ultraviolet visible near infrared (UV-Vis-NIR) spectrum was recorded to study the optical transparency of the grown crystal. The thermogravimetric (TG) and differential thermal (DTA) analyses revealed the thermal stability of the sample. The presence of second harmonic generation (SHG) for the grown crystal was confirmed by Kurtz-Perry powder technique.

EPHX1 gene polymorphisms in alcohol dependence and their distribution among the Indian populations.

BACKGROUND: The microsomal epoxide hydrolase is a phase II enzyme of the biotransformation. The human epoxide hydrolase 1 (EPHX1) gene lies in the chromosomal region 1q42.1 and exhibits polymorphism. Two single nucleotide polymorphisms (SNPs) have been described in the coding region of the EPHX1 gene that produces two protein variants. SUBJECTS AND METHODS: A total of 604 samples belonging to 13 Indian populations were included in this study. Based on the DSM-IV criteria, 184 individuals from Kota population were classified into alcoholism cases (100) and controls (84). Genotypes of Tyr113His and His139Arg polymorphisms in the EPHX1 gene were determined using PCR and sequencing. Associations were tested using Pearson's χ(2) test and haplotype analyses. RESULTS: We found significant association between EPHX1 gene Tyr113His polymorphism and alcoholism in the Kota population (T vs. C: OR = .615, 95% CI = .399-.949, p = .027; TT vs. CC + CT: OR = .536, 95% CI = .297-.969, p = .038). The very slow activity haplotype CA (113His-139His) was also found to be associated with alcohol dependence (p = .048). Analysis of additional populations demonstrated that the Tyr113His polymorphism significantly deviated from Hardy-Weinberg equilibrium in four populations but only one population deviated for the His139Arg locus. All populations shared the four possible two-site haplotypes. Linkage disequilibrium between these two loci was not significant in any of the population studied. CONCLUSION: EPHX1 gene polymorphisms and haplotypes are associated with an increased risk for alcoholism in the Kota population. This is the first report from India that will serve as a template for future investigations of the prevalence of EPHX1 alleles in association with various clinical entities.