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Lalji Singh

Publications and source records attributed to Lalji Singh.

At least 37 records · Page 2Linked to original sources
PubMed2006

Missense mutations in the BMP15 gene are associated with ovarian failure.

Premature ovarian failure (POF) is an unexplained amenorrhoea (>6 months) with raised levels of gonadotropins (FSH>40 U/L) occurring before the age of 40 years. Recent studies have elucidated the role of oocyte derived growth factors (BMP15 and GDF9) in maintenance of folliculogenesis, granulosa cell (GC) proliferation and overall fertility. Our recently published work showed presence of two rare missense variants in the GDF9 gene associated with ovarian failure (Dixit et al. 2005, Menopause 12:749-754). The present case-control study has been structured to establish the role of BMP15 germline status associated with ovarian failure. Sequence analysis of the coding region of the BMP15 gene was carried out in a cohort of women with POF (n=133), primary amenorrhoea (n=60), and secondary amenorrhoea (n=9) compared with control females (n=197). This study revealed a total of 18 germline variants in the coding region of BMP15 gene, including 16 novel variants. These novel variants include one intronic variant, one 3' flanking variant, one silent variant, and 13 missense variants. Eleven missense variants were present only in cases with complete absence in the control females. The remaining two missense variants viz. c.308A>G (p.Asn103Ser) and c.788_789insTCT (p.Leu263_Arg264insLeu) were present both in the cases and in the controls. The c.788_789insTCT variant was significantly higher in primary amenorrhoea cases than in the controls (Fisher's exact test, P=0.034). Three frequent variants c.-9C>G, c.308A>G, and c.852C>T were chosen for haplotyping. The haplotype G-G-C was found to be significantly associated with ovarian failure (P=0.0075). In a nutshell, the BMP15 gene is highly associated with etiology of ovarian failure.

Adolescent↗
PubMed2006

Genetic profile of nine autosomal STR loci among Halakki and Kunabhi populations of Karnataka, India.

POPULATION: Blood samples were collected from a total of 84 healthy and unrelated Halakki (44) and Kunabhi (40) populations, with their informed written consent. The geographic location of the sampled area is shown in Fig. 1. Both the populations are endogamous, and they belong to Dravidian linguistic family. Halakki is a tribal group having a population size of approximately 3383. They claim that they originally belong to Gujarat and Rajasthan, and migrated through Andhra Pradesh to Karnataka. Kunabhi is also a tribal population, who are approximately 35,214 in number. The male Kunabhi can be identified by their tattoo marks. A necklace is the symbol of married women. They were hunters and gatherers, but at present they practice agriculture.

DNA Fingerprinting↗
PubMed2006

A simple and inexpensive molecular method for sexing and identification of the forensic samples of elephant origin.

The population of the Asian elephant is being dramatically reduced due to poaching of the ivory from the male. As poaching occurs in remote forests, it often takes weeks or longer for it to be discovered and it is therefore often very difficult to determine the sex of the decomposed body. Data suggest that in the recent past, over 2000 male elephants have been poached in South India. We have developed a technique based on molecular markers to determine that the carcass is an elephant and that it is a male. Using DNA sequence information from Genbank, we have developed two primer pairs: one for the mitochondrial DNA (mtDNA) and the other for the sex-determining region of Y chromosome (SRY) gene of the Indian elephant. After PCR amplification of known elephant DNA, we found that the mtDNA was common in both males and females, whereas the SRY-specific amplicon was observed only in the male.

Animals↗
PubMed2005

Recurrent early pregnancy loss and endothelial nitric oxide synthase gene polymorphisms.

OBJECTIVE(S): Studies on the relation between endothelial nitric oxide synthase (eNOS) activity in implantation and maintenance of pregnancy highlights the importance of eNOS gene polymorphisms in recurrent early pregnancy loss (REPL). We investigated the relationship between idiopathic REPL and polymorphisms in eNOS among South Indian women. METHODS: A case-control study comprising 145 females with REPL and 99 control females. The polymorphisms studied include a 27 bp intron 4 repeat, Glu298Asp variation of exon 7 and a novel 140 A --> G polymorphism in intron 6. A polymerase chain reaction-based di-deoxy dye terminator sequencing method was used for genotyping. RESULTS: A novel A --> G polymorphism was identified in intron 6. The more frequent b allele of intron 4 repeat was present at a frequency of 0.84 in cases as compared to 0.86 in controls (O.R 1.17); the G allele of exon 7 coding for the wild-type glutamate containing isoform was present at a frequency of 0.79 in cases and 0.83 in controls (O.R 1.30, CI 0.6-2.8). The intron 6 variant A allele was present at a frequency of 0.58 in cases and 0.45 in controls (O.R 0.59, CI 0.33-1.08). Overall, the polymorphism in intron 6, in homozygous condition, exhibited a significant association to the risk of REPL (O.R 0.43, CI 0.21-0.89), P: 0.021). CONCLUSIONS: The present study identifies and validates a novel polymorphism in the eNOS gene which was found associated with the risk of REPL.

Abortion, Habitual↗
PubMed2005

Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure.

OBJECTIVE: To establish the risk associated with mutations in the coding region of GDF9 gene in Indian women with ovarian failure. DESIGN: This case-control study was designed for mutational analysis of the GDF9 coding region in a cohort of women with premature ovarian failure (n = 127), primary amenorrhea (n = 58), and secondary amenorrhea (n = 10) compared with controls (n = 220). RESULTS: This case-control study revealed eight mutations in the GDF9 gene, including five novel mutations: c.1-8C>T, c.199A>C (p.Lys67Glu), c. 205C>T, c.646G>A (p.Val216Mat), and c.1353C>T, and three documented mutations: c.398-39C>G, c.447C>T, and c.546G>A. Missense mutation c.199A>C was present in 4 of 127 premature ovarian failure (POF) cases and 1 of 10 secondary amenorrhea cases. The c.646G>A mutation was present in two POF cases. Both missense mutations were absent in controls. Genotype distribution of c.447C>T was significantly different in POF cases than controls (chi(2) = 5.93, P = 0.05). We chose two frequent single-nucleotide polymorphisms (c.398-39C>G, c.447C>T) for haplotyping and found that the C-T haplotype was significantly higher in patients (P = 0.03), whereas the C-C haplotype was representative of the control group. CONCLUSIONS: We report two rare missense mutations, c.199A>C and c.646G>A, which are associated with ovarian failure. The presence of the c.447>T mutation might indicate a higher risk for POF. Haplotype C-T was significantly associated with ovarian failure, whereas the C-C haplotype was representative of the control group.

Adolescent↗
PubMed2005

Chromosome inversions and a novel chromosome insertion associated with recurrent miscarriages in South India.

The aim of the present study was to investigate the contribution of chromosomal abnormalities and the frequency of a particular type of aberration in couples of South Indian origin with recurrent miscarriages. A total of 160 couples with recurrent miscarriages were analyzed using Giemsa-Trypsin-Giemsa (GTG) banding and Fluorescence in situ hybridization (FISH) wherever necessary. Chromosomal abnormalities were detected in 18 individuals representing 11.25% of the samples analyzed. Present study describes majority of the cases with chromosome inversions found to be common among the referred couples. Among the abnormal karyotypes, we report for the first time an unique case of chromosome insertion in a woman with the karyotype 46,XX,ins(12;6)(q24.2;q23q25) associated with recurrent miscarriages. The overall incidence of abnormalities and the predominance of chromosome inversions indicates to physicians that routine chromosome analysis of infertile couples of South Indian origin should be essentially considered before the planning of Intra Cytoplasmic Sperm Injection (ICSI), and also the priorities for cytogenetic screening in individual cases should be established.

Abortion, Habitual↗
PubMed2005

Reconstructing the origin of Andaman Islanders.

The origin of the Andaman "Negrito" and Nicobar "Mongoloid" populations has been ambiguous. Our analyses of complete mitochondrial DNA sequences from Onges and Great Andaman populations revealed two deeply branching clades that share their most recent common ancestor in founder haplogroup M, with lineages spread among India, Africa, East Asia, New Guinea, and Australia. This distribution suggests that these two clades have likely survived in genetic isolation since the initial settlement of the islands during an out-of-Africa migration by anatomically modern humans. In contrast, Nicobarese sequences illustrate a close genetic relationship with populations from Southeast Asia.

Africa↗
PubMed2005

Different population histories of the Mundari- and Mon-Khmer-speaking Austro-Asiatic tribes inferred from the mtDNA 9-bp deletion/insertion polymorphism in Indian populations.

Length variation in the human mtDNA intergenic region between the cytochrome oxidase II (COII) and tRNA lysine (tRNA(lys)) genes has been widely studied in world populations. Specifically, Austronesian populations of the Pacific and Austro-Asiatic populations of southeast Asia most frequently carry the 9-bp deletion in that region implying their shared common ancestry in haplogroup B. Furthermore, multiple independent origins of the 9-bp deletion at the background of other mtDNA haplogroups has been shown in populations of Africa, Europe, Australia, and India. We have analyzed 3293 Indian individuals belonging to 58 populations, representing different caste, tribal, and religious groups, for the length variation in the 9-bp motif. The 9-bp deletion (one copy) and insertion (three copies) alleles were observed in 2.51% (2.15% deletion and 0.36% insertion) of the individuals. The maximum frequency of the deletion (45.8%) was observed in the Nicobarese in association with the haplogroup B5a D-loop motif that is common throughout southeast Asia. The low polymorphism in the D-loop sequence of the Nicobarese B5a samples suggests their recent origin and a founder effect, probably involving migration from southeast Asia. Interestingly, none of the 302 (except one Munda sample, which has 9-bp insertion) from Mundari-speaking Austro-Asiatic populations from the Indian mainland showed the length polymorphism of the 9-bp motif, pointing either to their independent origin from the Mon-Khmeric-speaking Nicobarese or to an extensive admixture with neighboring Indo-European-speaking populations. Consistent with previous reports, the Indo-European and Dravidic populations of India showed low frequency of the 9-bp deletion/insertion. More than 18 independent origins of the deletion or insertion mutation could be inferred in the phylogenetic analysis of the D-loop sequences.

Asia, Southeastern↗
PubMed2005

Molecular insight into a wildlife crime: the case of a peafowl slaughter.

We report a recent case in which a wildlife warden had suspected that some people had killed and cooked a peacock. Cooked meat, intestine of bird and the wooden block used for chopping were seized from the site of crime and forwarded to our laboratory for DNA testing. Mitochondrial cytochrome b sequence analysis revealed that the cooked meat and remnants of the bird were of a chicken, but the DNA obtained from the wooden block was of an Indian Peafowl (Peacock) testifying that the wooden chopping block was used to chop the meat of an endangered bird, thus bringing to light a wildlife crime.

Animals↗
PubMed2005

A mouse gene encoding a novel member of the WD family of proteins is highly conserved and predominantly expressed in the testis (Wdr13).

Wdr13, a novel member of the WD family of proteins and the mouse homolog of WDR13 is localized to the locus XA1.1 and is predominantly expressed in the testis. The expression begins at the early stages of gonadal development and is maintained throughout the adult life with a predominant expression in the germ cells of adult testis. RNA in situ hybridization on the testis and brain sections indicated a cytoplasmic expression of the transcript. The alternatively spliced transcripts of the gene are generated by different methods and showed a differential pattern of expression, suggesting functional diversity. The expression of the gene in the unfertilized egg and in the neural stem cells indicated the functional significance of the gene from the early stages of development. The nuclear localization of the mouse WDR13 protein suggested a regulatory function. Evolutionary analysis of the gene indicated an extensive functional conservation across diverse species. Comparison of the genomic organization of the different homologs revealed a varied organization in the invertebrate homolog and the retention of the functionally significant introns in the same.

Alternative Splicing↗
PubMed2005

Differential protein expression in human gliomas and molecular insights.

Gliomas are the most common of the primary intracranial tumors with astrocytomas constituting about 40%. Using clinically and histologically assessed astrocytomas, we have studied their protein profiles using a two-dimensional gel electrophoresis-mass spectrometry approach and identified differentially expressed proteins which may be useful molecular indicators to understand these tumors. Examination of the protein profiles of 27 astrocytoma samples of different grades revealed 72 distinct, differentially expressed proteins belonging to various functional groups such as cytoskeleton and intermediate filament proteins, heat shock proteins (HSPs), enzymes and regulatory proteins. Based on the consistency of their differential expression, 29 distinct proteins could be short-listed and may have a role in the pathology of astrocytomas. Some were found to be differentially expressed in both Grade III and IV astrocytomas while others were associated with a particular grade. A notable observation was underexpression of Prohibitin, a potential tumor suppressor protein, Rho-GDP dissociation inhibitor, Rho-GDI, a regulator of Rho GTPases and HSPs as well as destabilization of glial fibrillary acidic protein, GFAP, major protein of the glial filaments, in Grade III malignant tumors. We attempt to explain glioma malignancy and progression in terms of their combined role.

Astrocytoma↗
PubMed2005

Prevalence of chromosome defects in azoospermic and oligoastheno-teratozoospermic South Indian infertile men attending an infertility clinic.

The prevalence of chromosomal abnormalities in azoospermic and oligoastheno-teratozoospermic infertile men of South Indian origin undergoing assisted reproductive technologies was evaluated. In addition, the study aimed to investigate new abnormal karyotypes involving autosomes in azoospermia and sex chromosomes in oligoastheno-teratozoospermic individuals that are supposed to be rare. Metaphase chromosomes of 744 infertile men, including 272 men with azoospermia and 472 men with oligoastheno-teratozoospermia (OAT), were analysed using Giemsa-trypsin-Giemsa banding and fluorescence in-situ hybridization (FISH) wherever necessary. Chromosomal abnormalities were observed in 59 (7.9%) individuals of the total studied population. Among these, 30 out of 272 (11.0%) azoospermic men and 29 out of 472 (6.1%) infertile men with OAT showed chromosomal abnormalities. A strong and statistically significant association (OR = 1.89; P = 0.0235) of chromosomal abnormalities and sex chromosome abnormalities (OR = 4.29; P = 0.001) with azoospermia when compared with OAT was observed. In addition, six autosomal abnormalities associated with azoospermia and two abnormalities involving Y chromosome, which include a novel karyotype (mos 46,XY/51,XYYYYYY) in OAT individuals, were detected.

Adult↗
PubMed2005

Screening of the galactose-1-phosphate uridyltransferase gene in Indian women with ovarian failure.

The present study was aimed at mutational screening of the gene coding for galactose-1-phosphate uridyltransferase in females with premature ovarian failure within an Indian population. A case-control-based study approach was used. It included females with premature ovarian failure (n = 108), primary amenorrhoea (n = 37) and secondary amenorrhoea (n = 9), and a control group of 136 women with a normal ovarian pattern. Gene sequencing analysis for the presence of mutations in the promoter and the coding regions of GALT has shown the absence of any mutation. A hexanucleotide deletion was found in the third intronic region of GALT in both cases and controls. These data support the hypothesis that there is no significant association between GALT mutations and ovarian failure, and hence the present authors conclude that there is no relationship between ovarian failure and GALT polymorphisms in Indian women.

Adult↗
PubMed2005

Novel X-chromosomal defect associated with abnormal ovarian function.

Abstract Premature ovarian failure (POF) may be idiopathic or may be associated with genetic or autoimmune disorders. It is well known that chromosomal defects can impair ovarian development and its function. It is estimated that X-chromosome abnormalities occur in 10-25% of women with abnormal ovarian function. Of these, the common chromosome defects reported are either true Turner's karyotype or its variants. We describe a novel X-chromosome aberration in a woman with primary amenorrhea. Cytogenetic and fluorescence in situ hybridization analysis revealed a short-arm deletion of X-chromosome as a Turner's variant [mos,45,XO/46,Xdel(X)(p11.1-p22.3)]. This interesting and rare case with unique X-chromosome defect reveals an additional mechanism for the cause of POF.

Adult↗
PubMed2005

Microsatellite diversity in Andhra Pradesh, India: genetic stratification versus social stratification.

DNA samples of 948 individuals belonging to 27 populations from southern Andhra Pradesh were analyzed for nine AmpFlSTR Profiler Plus loci. The nature and extent of genomic diversity within and between these populations have been examined with reference to socioeconomic and geographic affiliations. The results suggest that the average heterozygosity is uniformly high in these populations (> 0.80) and that the patterns of allele distributions are similar across the populations. The value of the coefficient of gene differentiation and the AMOVA and structure analysis results suggest that these populations are highly homogeneous. The neighbor-joining tree constructed using either D(A) or F(ST) distances suggests no intelligible pattern of population clusters based on ethnohistoric or geographic affiliations. All these observations suggest either a common recent origin of these populations or extensive gene flow across the populations that erased the original genetic differences. Given strict endogamy, the latter explanation can hold only if there has been unauthorized or unrecognized gene flow transecting the social boundaries. Nevertheless, the regression plot of average heterozygosity versus distance from the centroid (Rii), based on Harpending and Ward's (1982) model, and the genetic distances computed between different hierarchical groups within Andhra Pradesh tend to support this conjecture. Overall, the results suggest lack of a significant degree of genetic stratification that is consistent with social stratification in Andhra Pradesh. Furthermore, the neighbor-joining tree based on comparative data from other Indian and continental populations brings out a single and compact cluster of all the Andhra populations that is clearly separated from the rest.

Alleles↗
PubMed2004

Association of CYP1A1 gene polymorphism with recurrent pregnancy loss in the South Indian population.

BACKGROUND: We investigated the relationship between idiopathic recurrent pregnancy loss (RPL) and genetic polymorphisms in phase I and phase II detoxification genes which include CYP1A1, CYP2D6, GSTM1, GSTP1 and GSTT1. METHOD: A case-control study comprised 160 females with RPL and 63 healthy controls with a successful reproductive history. RESULTS: The CYP1A1 variant allele was present at frequencies of 0.61 and 0.44 in cases and controls, respectively (odds ratio=1.93; P=0.023, 95% confidence interval 1.10-3.38). The CYP2D6 variant allele was present at a frequency of 0.17 in females with RPL, while in the control population the frequency was 0.16. The GSTM1 and GSTT1 null genotypes were present at frequencies of 0.39 and 0.26 in RPL cases, whereas in controls the frequencies were 0.37 and 0.17, respectively. The mutant GSTP1 frequencies in case and control women were 0.38 and 0.40, respectively. We report a significant association of the CYP1A1*2A allele with RPL which is confirmed by logistic regression analysis. No association was observed for the other polymorphisms or in their combinations studied. CONCLUSIONS: The present study suggests the occurrence of the CYP1A1*2A allele as a probable risk factor in idiopathic recurrent miscarriages.

Abortion, Habitual↗
PubMed2004

A novel microsatellite (STR) marker for forensic identification of big cats in India.

India is the home to five of the eight majestic big cats of the world. The three major big cats namely, lion, tiger, and leopard are listed in the Schedule I of the Indian Wildlife Protection Act, 1972. Apart from the severe loss of the habitat, these are continuously facing the danger of extinction mainly due to poaching and hunting for their body parts, which are being greatly valued by apothecaries marketing traditional Chinese medicines. With the advent of polymerase chain reaction (PCR), DNA-based markers have emerged as major tools in the arena of wildlife forensics. Microsatellites (short tandem repeats, STRs) are markers of choice because of their polymorphic and co-dominant nature. These strictly follow the Mendelian inheritance and are highly reproducible. We have identified a new microsatellite (STR) locus Ple 46, which shows amplification in a species-specific manner (size of STR) in all the members of the family felidae studied here. This PCR-based, non-invasive method opens a new avenue to forensic identification of big cats.

Animals↗