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Item Many OX PHOS and replication factor mRNAs target mitochondria through specific binding to the organelle surface, independent of cotranslational protein import(The Indian Academy of Sciences, 2023-02) ADHYA, SAMIT; BANIK, MILONA large number of nucleus-encoded messenger RNAs (mRNAs) encoding proteins involved in oxidative phosphorylation have been found to be associated with mitochondria in vivo, indicating organelle-specific mRNA targeting. However, the identification of mitochondrion-bound mRNA (Mtb-RNA) has traditionally relied on cumbersome isolations of polysomes from a large number of input cells and is therefore biased in favour of mRNAs associated through nascent targeting peptides emerging from the polysome during cotranslational import of their encoded proteins, and tends to ignore sequence-directed mRNA targeting. We have, therefore, sought to identify and quantify Mtb-RNAs rapidly in small numbers of cells, independently of their polysomal status. We isolated Mtb-RNAs from tissue-cultured cells under different conditions and assayed them by endpoint or real-time polymerase chain reaction (RT-PCR). We observed that (i) different Mtb-RNAs are differentially affected by cycloheximide-induced polysome arrest, indicating possible artifacts of the use of this translation elongation inhibitor; (ii) several Mtb-RNAs have direct affinity for the mitochondrial surface in vitro, indicating the possibility of targeting through mRNA recognition by surface-bound RNA-binding proteins (RBP); and (iii) mRNA–mitochondrion interactions are stabilized by formaldehyde crosslinking. Our results reveal the importance of sequence-directed targeting of mRNAs to mitochondria.Item miR-7160 inhibits gastric cancer cell proliferation and metastasis by silencing SIX1(The Indian Academy of Sciences, 2024-08) MENG, MENG; GUAN, GUOXIN; LIU, XINGMING; SUN, WEI; CUI, XINYE; FU, SAIYA; LUO, FUWENUpregulation of homeoprotein SIX1 in gastric cancer (GC) is related to tumour proliferation and invasion. MicroRNA-7160 (miR-7160) is a homeoprotein SIX1-targeting miRNA that downregulates miR-7160, leading to cancer development. Total gastric cancer samples were collected from six patients, and relative expression levels of SIX1 mRNA and miRNAs were analysed by qRT-PCR. To evaluate the regulation of SIX1 by miR-7160, pGL3-SIX1-mut, pGL3-SIX1, and miR-7160 mimics transfected into cells using lipofec- tamine 2000. After transfection, proliferation and apoptosis in cultured cells were assessed using the nuclear TUNEL staining and CCK8 reagent, respectively. We demonstrated that the downregulation of miR-7160 in human gastric cancer cells is related to the upregulation of SIX1 mRNA. In gastric cancer cell lines, miR-7160 overexpression could downregulate the expression and inhibit cancer cell proliferation and growth in vitro. However, overexpression of miR-7160 did not increase gastric cancer cell apoptosis. In vitro downregulation of SIX1 decreased vimentin, N-cadherin, and other EMT-related gene expression and increased E-cadherin expression. In brief, miR-7160, by targeting SIX1, inhibits gastric cancer proliferation and cell growth in vitro, which provides an idea for introducing a new treatment option for gastric cancer.Item Association study of common KLF1 variants with Hb F and Hb A2 levels in ?-thalassaemia carriers of Portuguese ancestry(The Indian Academy of Sciences, 2024-10) MANCO, LICI ?NIO; BENTO, CELESTE; RELVAS, LUI ?S; MAIA, TABITA; RIBEIRO, M. LETI ?CIAKruppel-like factor 1 (KLF1) is an essential erythroid-specific transcription factor. Several reports have shown that KLF1 gene mutations are associated with increased levels of Hb F and Hb A 2. However, scarce population studies have analysed common KLF1 variations. This study examines the potential association with Hb F and Hb A2 levels in b-thalassemia (b-thal) carriers of Portuguese ancestry of the four common KLF1 gene variants: -251C[G (rs3817621) and -148G[A (rs79334031), in the promoter region; and c.115A[C (p.Met39Leu) (rs112631212) and c.304T[C (p.Ser102Pro) (rs2072597), in exon 2. Ninety-two Portuguese b-thal carriers (43 males and 49 females) aged 2 to 77 years old (mean 32.55 years) were engaged in the study. Hb F levels range from 0.2 to 12.5% and Hb A 2 was above the normal level, ranging from 3.6 to 6%. The Hb A 2 and Hb F levels were determined by high-performance liquid chromatography. Single-nucleotide polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length poly- morphism (PCR-RFLP) method. Minor allele frequencies for SNPs rs3817621 (G), rs79334031 (A), rs112631212 (C) and rs2072597 (C) were 0.196, 0.016, 0.011 and 0.169, respectively. Basic simple linear regression in the total population showed no significant associations with the levels of Hb F (P[0.05). For the low-frequency variant -148A, a statistically significant association was found with increased levels of Hb A2 (b = 0.855; P = 0.017). In conclusion, an association signal with Hb A2 levels was observed for the variant -148A[G (rs79334031). The complex pattern of SNP interactions related to their influence on the KLF1 transcriptional activity may explain the absence of association with Hb F levels.Item COQ7 splice site variant causing a spastic paraparesis phenotype in siblings(The Indian Academy of Sciences, 2024-07) SAIT, HASEENA; PANDEY, MANMOHAN; PHADKE, SHUBHA R.The COQ7 gene is one of the causative genes for primary COQ10 deficiency-related disorders. OMIM-related phenotypes include severe encephalo-myo-nephrocardiopathy and distal hereditary motor neuronopathy. In the present study, we performed the exome sequencing analysis on the proband of a single family with two siblings affected by hereditary spastic paraparesis (HSP). Segregation analysis was conducted on the affected siblings and parents using the Sanger sequencing. In silico secondary and tertiary pre-mRNA structure analysis and protein modelling were carried out. Exome sequencing identified a homozygous splice site variant in the COQ7 gene (NM_016138.5: c.367?5G[A) in the proband. Sanger sequencing confirmed the homozygous status in the affected sibling and heterozygous status in both parents, consistent with autosomal recessive inheritance. In silico secondary and tertiary premRNA structure analysis and protein modelling predicted the deleterious nature of the variant. This case highlights a distinct intermediate phenotype of COQ7 related disorders comprising early-onset spastic paraparesis due to a novel splice site variant in the COQ7 gene. This expands the spectrum of clinical manifestations associated with COQ7 deficiency and underscores the importance of considering COQ7 gene mutations in the differential diagnosis of HSP.Item Detection of caudal type homeobox 1 (CDX1) gene methylated DNA, as a stool-based diagnostic biomarker in colorectal cancer(The Indian Academy of Sciences, 2024-06) ALMASI, SARINA; HAGHNAZARI, LIDA; HOSSEINI, SEYEDEH OZRA; REZVANI, NAYEBALIColorectal 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.Item A global evaluation of mitochondrial DNA diversity and distribution of dromedary, Camelus dromedarius from north-central Saudi Arabia(The Indian Academy of Sciences, 2024-07) BARDAKCI, FEVZI; ABDELGADIR, ABDELMUHSIN; ALAM, MD JAHOOR; BIYIK, HACI HALIL; SIDDIQUI, ARIF JAMAL; BADRAOUI, RIADH; ADNAN, MOHD; ALRESHIDI, MOUSA; KO, ATAKAN; SNOUSSI, MEJDIKnowledge of genetic variability within and among types and breeds of dromedary (Camelus dromedarius L.) can be a valuable asset in selective breeding of desirable characteristics and will shed light on their origin, dynamics of domestication, and dispersion. Variability in an 809 bp segment of the mtDNA genome was measured within and among dromedaries from eight indigenous and one exogenous breed from Ha’il in north-central Saudi Arabia. Sixteen mtDNA haplotypes were identified among 47 camels. Haplotypic diversity among breeds is high (Hd = 0.817); most of the AMOVA variance (55.05%) occurs within breeds. Phylogenetic comparison of these haplotypes with those obtained across their geographic range showed that most haplotypes were placed within the same cluster with ancient wild dromedaries and the two newly identified haplotypes in this study. The most prevalent haplotypes found in dromedaries from this area appear to be ancestral to most other dromedaries and differ from each other by only one SNP. These results support the hypothesis that the Arabian Peninsula is a hub of diversification for dromedaries.Item A novel intron variant in the prolactin gene associated with eggshell weight and thickness with putative alternative splicing patterns in chickens(The Indian Academy of Sciences, 2024-09) ALI, DHAFER A.; ALI, NIHAD ABDUL-LATEEF; ALJUBOURI, THAMER R. S.; AL-SHUHAIB, MOHAMMED BAQUR S.Raising Iraqi indigenous chickens (IIC) is restricted by their thin and low eggshell weights. Due to the importance of the prolactin (Prl) gene in regulating a wide range of egg production traits, this study assessed the potential genetic polymorphisms associated with Prl that may influence these traits. The polymorphism was examined in three Prl loci of the IIC breed (n = 120) in comparison with the standard Hyline breed (n = 120). The polymorphism of both breeds was associated with eggshell weight and thickness indices for 16 weeks, starting from the 44th to the 59th week. After genotyping three loci within Prl by polymerase chain reaction-single-stranded conformation polymorphism (SSCP) method, only one novel SNP was identified in intron 4, namely 129G [ A. The identified intron SNP exerted a significant association with both eggshell thickness and weight indices throughout the investigation period. Birds with GG genotype exhibited higher indices of eggshell thickness and weight than those with the GA and AA genotypes, respectively. The employed in silico tools predicted a remarkable ability for the identified SNP to alter the mRNA splicing pattern, which might be related to altered prolactin activity in birds having an alternative allele A. This study is the first to suggest the significance of this novel intron SNP in assessing eggshell traits in chickens.Item Identification of a novel mutation in the HACD1 gene in an Iranian family with autosomal recessive congenital myopathy, with fibre-type disproportion(The Indian Academy of Sciences, 2023-01) JABBARPOUR, NEDA; POORSHIRI, BITA; SAEI, HASSAN; BARZEGAR, MOHAMMAD; BONYADI, MORTAZACongenital fibre-type disproportion (CFTD) with myopathy, is a genetically heterogeneous disease in which there is relative hypotrophy of type-1-muscle-fibres compared to type-2-fibres on skeletal muscle biopsy. The classical characteristics of CFTD are infantile hypotonia and nonprogressive muscle weakness with a broad range of clinical manifestations. Pathogenic mutations in the HACD1 gene encoding 3-hydroxyacyl-CoA-dehydratase-1 have recently been reported to be associated with this disease. Whole-exome sequencing (WES) was conducted in a 12-year-old girl born to consanguineous parents from the Iranian-Azeri-Turkish population. She was diagnosed with congenital myopathy at the age of 4-month-old due to hypotonia and abnormal electromyography. DNAs were extracted from the blood samples of the proband and her parents, and subjected to PCR-Sanger-sequencing to confirm the WES result. WES data analysis identified a homozygous single nucleotide change (A[T) at position c.785-2 located in intron 6 of the HACD1 gene (NC_000010.11(NM_014241.4):c.785-2A[T). This novel mutation located at the splice-acceptor site is disturbing the splicing procedure. The absence of this mutation among our control group (100 normal healthy adults from the same ethnic group) and not being reported in any other population database confirms the pathogenicity of this mutation. Bioinformatics analysis also classified this variant as a pathogenic mutation. PCR-Sanger-sequencing data analysis confirmed the WES result in the proband and showed that the parents were carriers for the mutation. A substitution (NC_000010.11(NM_014241.4):c.785-2A[T) mutation resulted in the removal of the splicing acceptor site at the HACD1 gene. This pathogenic mutation is associated with CFTD disease.Item Assessment of the contribution of VDR and VDBP/GC genes in the pathogenesis of celiac disease(The Indian Academy of Sciences, 2024-09) BANERJEE, PRATIBHA; SINGH, HARINDER; TIWARI, PRIYANKA; SOOD, AJIT; MIDHA, VANDANA; SINGH, GURSEWAK; THELMA, B K; SENAPATI, SABYASACHIVitamin-D deficiency (VDD) is a global health concern. It is known to play a critical role in the immunomodulation, and thus, its metabolism could be investigated to unravel its contribution in common immune-mediated diseases, e.g., celiac disease (CD). Geno- typing of SNPs from vitamin D receptor (VDR) gene, such as rs11568820 (Cdx2) and rs2228570 (Fok1) using allele specific multiplex polymerase chain reaction (ASM-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respec- tively; and rs7041 and rs4588 of vitamin D binding protein (VDBP/GC) using PCR-RFLP were done in 969 subjects including CD cases (n=506) and controls (n=463). Genotype data for 86 CD and 712 controls for rs11568820 and rs7041 were retrieved from already published Immunochip genotype data. Serum concentration of vitamin-D and vitamin D binding protein (VDBP) were measured for 283 participants (98 CD and 185 controls). rs4588-A allele was identified as protective allele [OR=0.6(0.4–0.7), P\0.0001]. Significantly reduced serum level of vitamin-D was observed in CD patients [median=16.25 ng/mL, IQR (8.94–23.60)] than in controls [median=19.94 ng/mL, IQR (13.91–28.46)] with P=0.001. Notably, rs7041-GG, rs4588-CC, and 1F (GC) haplotype of VDBP/GC showed significant association (P\0.05) with reduced serum vitamin D level. We did not find any significant association with VDBP serum concentration. Significant vitamin D and VDBP level correlations were observed in controls (spearman r = 0.3, P=0.005). The present study highlights the significance of reduced vitamin-D serum level in CD. 1F variant of VDBP and lower vitamin-D levels contribute to CD. No correlation between vitamin-D and VDBP levels suggests that vitamin-D supplementation may improve vitamin-D levels but might not affect VDBP levels in CD subjects.Item First detection of endopolyploidy in tapetal cells and chromosomal anomalies in meiocytes of Viola pilosa cytotypes (2n=20) from Pir Panjal (Himalayas)(The Indian Academy of Sciences, 2023-01) IQBAL, TASIR; SHARMA, GEETAThe nine Viola pilosa Blume populations studied from Pir Panjal contained 20 chromosomes. This count is not reported so far in Indian populations. Currently, comparison of tapetal and meiotic cells revealed the existence of synchrony in different developmental phases. Young tapetal cells at prometaphase co-occurred with the pollen mother cells (PMCs) at diakinesis to metaphase, mature tapetal cells with disintegrated chromatin material co-occurred with tetrads and no tapetal cells were found at mature pollen stage. Cytological studies in young tapetal cells revealed most of these to be endopolyploid, with each having 40 chromosomes. While outnumbering somatic cells contained clear 40 chromosomes which seemed to be the outcome of endomitosis, a sizeable number of cells possessed 40 sticky chromosomes at metaphase. Later chromosomes are likely to form restitution nucleus. Mature tapetal cells, occurring singly/cytomictically connected (3.2–26.31%) or showing coalescence (10.5–22.8%), did not contain recognizable chromosomes. Instead, they were charac- terized by disintegrated nuclear content. Further, meiotic studies revealed that the present population contained all/outnumbering euploid cells (2n=20); many of which exhibited nearly regular behaviour. However, 6.5–26.9% meiocytes of eight populations and 47% cells of P-Khe population depicted aneuploidy/contained quadri-octavalents, with per cent pollen viabilities of these ranging from 38.6 to 49.9. Going by the normal tapetal development in V. pilosa, existence of various chromosomal anomalies seems to have accounted for the reduction in gametic fertility of this taxon.Item Association of polymorphisms of HSD11B1 and ACE genes with trachoma disease(The Indian Academy of Sciences, 2024-06) VALDEZ-VELAZQUEZ, LAURA L.; OCHOA-DI ?AZ-LO ? PEZ, HE ? CTOR; DELGADO-ENCIS, O IVA ? N; RANGEL-VILLALOBOS, HE ? CTOR; RODRI ?GUEZ-SA ? NCHEZ, IRA ? M P.; GARCI ?A-MIRANDA, ROSARIO; VELA ? ZQUEZ-RAMI REZ, DOIREYNER DANIEL; REYES-ME ? NDEZ, NANCY A.; BARAJAS-SAUCEDO, CARLOS EDUARDO; NEZ-FIERRO, MARGARITA L. MARTI ?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 polymor- phisms (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.Item Expanding the genetic and phenotypic spectrum of Baker–Gordon syndrome: a new de novo SYT1 variant(The Indian Academy of Sciences, 2024-07) COTRINA-VINAGRE, FRANCISCO JAVIER; RODRI ?GUEZ-GARCI ?A, MARI ?A ELENA; POZO-FILI ?U, LUCI ?A DEL; QUIJADA-FRAILE, PILAR; MARTI ?NEZ-AZORI ?N, FRANCISCOWe 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.Item A novel missense variant in PNLDC1 associated with nonobstructive azoospermia(The Indian Academy of Sciences, 2024-08) RAHIMIAN, MOUNESS; ASKARI, MASOMEH; SALEHI, NAJMEH; JAAFARINIA, MOJTABA; FOROUZANFAR, MOHSEN; ALMADANI, NAVID; RICCIO, ANDREA; TOTONCHI, MEHDIThe most severe type of male infertility is nonobstructive azoospermia (NOA), where there is no sperm in the ejaculate due to failure of spermatogenesis. The predictable frequency of NOA in the general population is one in 100 men. Genetic studies have recognized dozens of NOA genes. Most NOA aetiologies remain idiopathic. Monogenic mutations can be a reason for a part of idiopathic NOA cases. To address this, we studied the pedigree of a consanguineous family with three NOAs by a family-based exome sequencing. Our goal was to pinpoint the genetic variants responsible for idiopathic NOA to aid future clinical genetic diagnostics and treatment strategies. Bioin- formatics analysis followed by Sanger sequencing revealed that NOA patients were homozygous for a rare novel missense variant in PNLDC1 (NM_173516:exon9:c.710G[A;p.Gly237Asp). In silico, single-cell RNA sequencing data analysis and protein modelling demonstrated that PNLDC1, Gly237Asp resided in the conserved region of the CAF1 domain which could lead to local instability in the structure and alteration of protein phosphorylation site. We conclude that the novel missense PNLDC1 variant may affect meiosis and spermatogenesis, leading to NOA and the genetic cause of this idiopathic NOA family. Our result helps genetic counselling for idiopathic NOA cases and provides the occasion for more efficient diagnosis in the clinical setting.Item Germline genetic variants in a case of familial cancer: RAD51D and four other co-segregated variants(The Indian Academy of Sciences, 2024-10) BISWAS, SHRISTI; MANEKAR, SWATI; KANTHARIA, SHEHNAZ; BAKSHI, SONALCancer is a multifactorial, multi-step process of pathogenesis; however, in the case of familial cancers, genetic aetiology can play a significant role. Identifying genetic variants in cancer patients having a strong family history of cancer as well as their unaffected blood relatives can unravel their role in predisposition to cancer. Here, we report the findings of whole-exome sequencing in a patient (77/F) diagnosed with ovarian cancer and her daughters (61/F) and (59/F) who were diagnosed with breast and ovarian cancers along with her asymptomatic son (53/M). All the four family members show segregation of RAD51D (rs200564819). Other incidental findings ADAMTS13 (rs142572218) and SYCE1 (rs201873178) genetic variants in proband and son, and LIAS (rs546751789) and PDHA1 (rs747051654) genetic variants in son have also been reported.Item Efficient assembly of a synthetic attenuated SARS-CoV-2 genome in Saccharomyces cerevisiae using multi-copy yeast vectors(The Indian Academy of Sciences, 2024-02) SINGH, ABHISHEK KUMAR; GOAR, HARSH; VASHIST, NIKITA; SINHA, PRAKASH; BACHHAWAT, ANAND KUMARSaccharomyces cerevisiae has been demonstrated to be an excellent platform for the multi-fragment assembly of large DNA constructs through its powerful homologous recombination ability. These assemblies have invariably used the stable centromeric single copy vectors. However, many applications of these assembled genomes would benefit from assembly in a higher copy number vector for improved downstream extraction of intact genomes from the yeast. A review of the literature revealed that large multi-fragment assemblies did not appear to have been attempted in multicopy vectors. Therefore, we devised a toolkit that would enable one to seamlessly transition with the same assembling fragments between a single copy and a multicopy vector. We evaluated the assembly of a 28 kb attenuated SARS- CoV-2 genome (lacking the N gene) from 10 fragments in both single copy and multicopy vector systems. Our results reveal that assembly was comparably efficient in the two vector systems. The findings should add to the synthetic biology toolkit of S. cerevisiae and should enable researchers to utilize any of these vector systems depending on their downstream applications.Item Foetal haemoglobin elevation, unfavourable prognosis, and protective role of genetic variants HBG2rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 in children with ALL(The Indian Academy of Sciences, 2024-04) BORRAYO-LO ? PEZ, FRANCISCO JAVIER; IBARRA-CORTE ? S, BERTHA; PEREA-DI ?AZ, FRANCISCO JAVIER; MUN ? OZ-ZU ? N ? IGA, ABRIL IXCHEL; MONTOYA-FUENTES, HE ? CTOR; SOTO-PADILLA, JANETH MARGARITA; TORRE, LOURDES DEL CARMEN RIZO-DE LAIn 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), Kru ?ppel-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 b-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.Item Estimation of genetic diversity of the exotic Indian trout populations by using microsatellite markers(The Indian Academy of Sciences, 2024-02) DEVAA, WALTER; PANNEERSELVAM, VIMAL; UTHANDAKALAIPANDIAN, RAMESHRainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta fario) are popular salmonid species that are reared for sport and recreational activities worldwide. In India, they were introduced and successfully established in the late 19th and early 20th centuries by the European settlers. However, until now, no studies have analysed the genetic integrity of wild trout populations in India. Therefore, this study aimed to analyse the genetic integrity of the wild rainbow trout populations from south India, one wild rainbow trout population from north India, and one wild brown trout population from north India. Genetic diversity studies revealed low genetic diversity in all the population with genetic bottlenecks in two trout populations from south India and disruption of alleles in the populations from north India. The results showed that the south Indian trout populations are in a comparatively poor condition than the north Indian trout populations, and stocking efforts have recently been carried out to enhance the genetic diversity of south Indian trout populations.Item Characters of the MOCA family in wheat and TaMOCA1 function in salt stress tolerance(The Indian Academy of Sciences, 2024-02) QIN, YUXIANG; CUI, PING; ZHANG, BAO; WANG, YUNINGMOCA1 encodes the last key glucuronosyltransferase for ionic stress sensor glycosyl inositol phosphoryl-ceramide (GIPCs) biosynthesis in Arabidopsis, which indicates that the MOCA gene family play important role in plant tolerance to salt stress. However, the isolation and function of MOCAs in staple crops have not been reported and the downstream targets of MOCAs in salt stress tolerance signalling pathway are not clear. In this study, we identified 110 MOCA genes in wheat which were classified into five clades and they differed in gene structure, protein length, conserved motifs and expression profiles in different tissues and under salt stress. TaMOCA1 was selected for further functional study in response to salt stress. TaMOCA1 was rapidly induced by NaCl treatment. The 35S::TaMOCA1-GFP construction showed the cell nucleus and cytoplasm location in wheat protoplast. TaMOCA1 over-expressing Arabidopsis seedlings formed longer primary roots and more lateral roots than the wild type ones under 50 mM NaCl treatment. The over-expressing Arabidopsis had higher expression levels of HKT1, but lower expression levels of NHX1 and SOS genes than the wild type. Also, the transgenic plants had higher SOD activity and lower MDA content than the wild Arabidopsis seedling under salt stress. These results may indicate that TaMOCA1 increases salt stress tolerance through decreasing Na? loading from the xylem parenchyma cells to the xylem via SOS1 and HKT1, hence lowering root-to-shoot deliveryItem Special clinical entity with 15q26 deletion: a novel case report(The Indian Academy of Sciences, 2024-05) LIU, WEI-LIANG; LI, FANG; LIU, LU; AI, RONGIn 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 indi- viduals 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.Item Genetic characterization and linkage analysis of spotted leaf 6, liguleless and lax panicle traits in mutant rice(The Indian Academy of Sciences, 2024-04) MATIN, MOHAMMAD NURUL; LEE, KYUNG EUN; KANG, SANG GUPhenotypic 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 F 2 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.