• Volume 94, Issue 4

December 2015,   pages  559-809

• In Remembrance: Mary Frances Lyon

• Mary Lyon’s X-inactivation studies in the mouse laid the foundation for the field of mammalian dosage compensation

• Weird mammals provide insights into the evolution of mammalian sex chromosomes and dosage compensation

The deep divergence of mammalian groups 166 and 190 million years ago (MYA) provide genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. With encouragement from the founder of the field, Mary Lyon, techniques in cytogenetics and molecular biology were progressively adapted to characterize the sex chromosomes of kangaroos and other marsupials, platypus and echidna—and weird rodent species. Comparative gene mapping reveals the process of sex chromosome evolution from their inception 190 MYA (they are autosomal in platypus) to their inevitable end (the Y has disappeared in two rodent lineages). Our X and Y are relatively young, getting their start with the evolution of the sex-determining 𝑆𝑅𝑌 gene, which triggered progressive degradation of the Y chromosome. Even more recently, sex chromosomes of placental mammals fused with an autosomal region which now makes up most of the Y. Exploration of gene activity patterns over four decades showed that dosage compensation via X-chromosome inactivation is unique to therian mammals, and that this whole chromosome control process is different in marsupials and absent in monotremes and reptiles, and birds. These differences can be exploited to deduce how mammalian sex chromosomes and epigenetic silencing evolved.

• Divergent actions of long noncoding RNAs on X-chromosome remodelling in mammals and Drosophila achieve the same end result: dosage compensation

Organisms with heterochromatic sex chromosomes need to compensate for differences in dosages of the sex chromosome-linked genes that have somatic functions. In-depth cytological and subsequent biochemical and molecular studies on dosage compensation started with Mary F. Lyon’s proposal in early 1960s that the Barr body in female mammalian somatic cells represented one of the randomly inactivated and heterochromatinized X chromosomes. In contrast, Drosophila was soon shown to achieve dosage compensation through hypertranscription of single X in male whose chromatin remains more open. Identification of proteins that remodel chromatin either to cause one of the two X chromosomes in somatic cells of very early female mammalian embryos to become condensed and inactive or to remodel the single X in male Drosophila embryos to a more open state for hypertranscription provided important insights into the underlying cellular epigenetic processes. However, the most striking and unexpected discoveries were the identification of long noncoding RNAs (lncRNAs), X- inactive specific transcript (Xist) in mammals and roX1/2 in Drosophila, which were essential for achieving the contrasting chromatin organizations but leading to similar end result in terms of dosage compensation of X-linked genes in females and males. An overview of the processes of X inactivation or hyperactivation in mammals and Drosophila, respectively, and the roles played by Xist, roX1/2 and other lncRNAs in these events is presented.

• Understanding sex determination in the mouse: genetics, epigenetics and the story of mutual antagonisms

Recent years have seen a rapid growth in mouse genetics resources that support research into fundamental mechanisms in organogenesis, including those controlling mammalian sex determinations. Numerous mouse mutants have shed light on molecular pathways of cell fate specification during gonadogenesis and the decision' as to whether testis or ovary development is achieved. These studies indicate substantial genetic complexity, characterized by redundancy, feedback loops, mutual antagonism between testis-determining and ovary-determining gene regulatory networks and a degree of plasticity in the fully differentiated state of the adult gonad that was not appreciated until conditional loss-of-function studies were performed. One challenge now is to understand how controlled epigenomic changes effect the now familiar sexually dimorphic transcriptomic profiles of the male and female gonads, firstly during primary sex determination, but also in the adult gonad, thereby regulating cellular behaviour during morphogenesis and maintaining the differentiated state.

• X-chromosome inactivation and escape

X-chromosome inactivation, which was discovered by Mary Lyon in 1961 results in random silencing of one X chromosome in female mammals. This review is dedicated to Mary Lyon, who passed away last year. She predicted many of the features of X inactivation, for e.g., the existence of an X inactivation center, the role of L1 elements in spreading of silencing and the existence of genes that escape X inactivation. Starting from her published work here we summarize advances in the field.

• Understanding gene expression in coronary artery disease through global profiling, network analysis and independent validation of key candidate genes

Molecular mechanism underlying the patho-physiology of coronary artery disease (CAD) is complex. We used global expression profiling combined with analysis of biological network to dissect out potential genes and pathways associated with CAD in a representative case–control Asian Indian cohort. We initially performed blood transcriptomics profiling in 20 subjects, including 10 CAD patients and 10 healthy controls on the Agilent microarray platform. Data was analysed with Gene Spring Gx12.5, followed by network analysis using David v 6.7 and Reactome databases. The most significant differentially expressed genes from microarray were independently validated by real time PCR in 97 cases and 97 controls. A total of 190 gene transcripts showed significant differential expression (fold change > 2, P < 0.05) between the cases and the controls of which 142 genes were upregulated and 48 genes were downregulated. Genes associated with inflammation, immune response, cell regula- tion, proliferation and apoptotic pathways were enriched, while inflammatory and immune response genes were displayed as hubs in the network, having greater number of interactions with the neighbouring genes. Expression of 𝐸𝐺𝑅1/2/3, 𝐼𝐿8, 𝐶𝑋𝐶𝐿1, 𝑃𝑇𝐺𝑆2, 𝐶𝐷69, 𝐼𝐹𝑁𝐺, 𝐹𝐴𝑆𝐿𝐺, 𝐶𝐶𝐿4, 𝐶𝐷𝐶42, 𝐷𝐷𝑋58, 𝑁𝐹𝐾𝐵𝐼𝐷 and 𝑁𝑅4𝐴2 genes were independently validated; 𝐸𝐺𝑅1/2/3 and 𝐼𝐿8 showed >8-fold higher expression in cases relative to the controls implying their important role in CAD. In conclusion, global gene expression profiling combined with network analysis can help in identifying key genes and pathways for CAD.

• Chalcone synthase genes from milk thistle (Silybum marianum): isolation and expression analysis

Silymarin is a flavonoid compound derived from milk thistle (Silybum marianum) seeds which has several pharmacological applications. Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoids; thereby, the identification of 𝐶𝐻𝑆 encoding genes in milk thistle plant can be of great importance. In the current research, fragments of 𝐶𝐻𝑆 genes were amplified using degenerate primers based on the conserved parts of Asteraceae 𝐶𝐻𝑆 genes, and then cloned and sequenced. Analysis of the resultant nucleotide and deduced amino acid sequences led to the identification of two different members of 𝐶𝐻𝑆 gene family, 𝑆𝑚𝐶𝐻𝑆1 and 𝑆𝑚𝐶𝐻𝑆2. Third member, full-length cDNA (𝑆𝑚𝐶𝐻𝑆3) was isolated by rapid amplification of cDNA ends (RACE), whose open reading frame contained 1239 bp including exon 1 (190 bp) and exon 2 (1049 bp), encoding 63 and 349 amino acids, respectively. In silico analysis of SmCHS3 sequence contains all the conserved CHS sites and shares high homology with CHS proteins from other plants. Real-time PCR analysis indicated that 𝑆𝑚𝐶𝐻𝑆1 and 𝑆𝑚𝐶𝐻𝑆3 had the highest transcript level in petals in the early flowering stage and in the stem of five upper leaves, followed by five upper leaves in the mid-flowering stage which are most probably involved in anthocyanin and silymarin biosynthesis.

• Statistical equivalent of the classical TDT for quantitative traits and multivariate phenotypes

Clinical end-point traits are usually governed by quantitative precursors. Hence, there is active research interest in developing statistical methods for association mapping of quantitative traits. Unlike population-based tests for association, family-based tests for transmission disequilibrium are protected against population stratification. In this study, we propose a logistic regression model to test the association for quantitative traits based on a trio design. We show that the method can be viewed as a direct extension of the classical transmission diequilibrium test for binary traits to quantitative traits. We evaluate the performance of our method using extensive simulations and compare it with an existing method, family-based association test. We found that the two methods yield comparable powers if all families are considered. However, unlike FBAT, which yields an inflated rate of false positives when noninformative trios with all three individuals’ heterozygous are removed, our method maintains the correct size without compromising too much on power. We show that our method can be easily modified to incorporate multivariate phenotypes. Here, we applied this method to analyse a quantitative endophenotype associated with alcoholism.

• Frequency of mutations in Mediterranean fever gene, with gender and genotype–phenotype correlations in a Turkish population

Familial Mediterranean fever (FMF) is the most common hereditary inflammatory periodic disease, characterized by recurrent episodes of fever, abdominal pain, synovitis and pleurisy. The aim of this study was to determine the frequency and distribution of Mediterranean fever (𝑀𝐸𝐹𝑉) gene mutations and to investigate the clinical characteristics and genotype–phenotype correlation in patients with FMF in Aydın, a province in western Anatolia, Turkey. Therefore, we retrospectively analysed 𝑀𝐸𝐹𝑉 gene mutations in 383 patients with suspected FMF and the clinical features of 327 among them. The 𝑀𝐸𝐹𝑉 gene mutations were investigated using the reverse dot-blot hybridization technique. We detected 26 different genotypes and 11 different mutations. The most common mutations in our cohort were p.M694V (41.15%), p.E148Q (20.35%), p.M680I(G/C) (12.39%) and p.R761H (9.73%). Abdominal pain (86.2%), fever (80.7%), arthralgia (57.2%), vomiting (36.1%), arthritis (34.6%), fatigue (31.5%), anorexia (22.9%) and chest pain (19.0%) were the most prevalent clinical features in our patients. This is the first study from Aydın in which the distribution of 𝑀𝐸𝐹𝑉 gene mutations and clinical features were evaluated in patients with FMF. We found that the most common mutation was p.M694V in our region, while the frequency of the p.R761H mutation was higher compared to other regions of Turkey with respect to extracted data from previous similar studies. Presented results supported the clinical findings in the literature that the homozygous p.M694V and compound heterozygous genotype were associated with more severe courses in FMF patients.

• Combined effect between two functional polymorphisms of SLC6A12 gene is associated with temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common epilepsy subtype with complex genetic structure. A recent study in four populations (Ireland, UK, Australia and Finland) reported an allelic association between betaine/GABA transporter-1 (𝐵𝐺𝑇-1 or 𝑆𝐿𝐶6𝐴12) and mesial temporal lobe epilepsy with hippocampal sclerosis. To demonstrate the association between 𝑆𝐿𝐶6𝐴12 gene polymorphisms and TLE, TaqMan method was used to genotype five single-nucleotide polymorphisms of 𝑆𝐿𝐶6𝐴12 gene in 358 TLE patients and 596 nonepileptic control subjects of Chinese Han origin. Real-time PCR was used to detect the effects of variations on gene expression associated with TLE. Though, the single-marker analysis did not demonstrate allelic association with TLE, rs542736–rs557881 interaction showed significant association. The 𝑆𝐿𝐶6𝐴12 expression levels in peripheral blood mononuclear cells were significantly higher in TLE patients than in control subjects and were correlated to rs542736 G–rs557881 A haplotypes. Our preliminary results suggested combined effect of two common polymorphisms on SLC6A12 gene may be associated with TLE, but the precise mechanism needs further investigation.

• Effect of lead pollution on fitness and its dependence on heterozygosity in Drosophila subobscura

Lead is one of the most present contaminants in the environment, and different species respond differently to this type of pollution. If combined with genomic stress, lead may act synergistically, causing significant decrease of fitness components. We used two genetically diverse Drosophila subobscura populations (regarding both putatively adaptive inversion and microsatellite loci polymorphisms) originating from two ecologically distinct habitats. To establish different levels of genome heterozygosity, series of intraline, intrapopulation and interpopulation crosses were made. The progeny were reared on a standard medium and a medium with 200 𝜇g/mL of lead acetate. Development time was significantly extended to all groups reared on lead. The progeny of intraline crosses showed significantly extended development time compared to all other groups. The obtained results suggest that genome heterozygosity reduces the effect of lead pollution.

• Variants in the interleukin-1 alpha and beta genes, and the risk for periodontal disease in dogs

Elevated levels of interleukin-1 (IL-1) have been shown to amplify the inflammatory response against periodontopathogenic bacteria. In humans, polymorphisms in the 𝐼𝐿1𝐴 and 𝐼𝐿1𝐵 genes are the most well-studied genetic polymorphisms associated with periodontal disease (PD). In contrast to human, there is a lack of knowledge on the genetic basis of canine PD. A case–control study was conducted in which a molecular analysis of dog 𝐼𝐿1𝐴 and 𝐼𝐿1𝐵 genes was performed. Of the eight genetic variants identified, seven in 𝐼𝐿1𝐴 gene and one in 𝐼𝐿1𝐵 gene, 𝐼𝐿1𝐴/1_g.388A>C and 𝐼𝐿1𝐴/1_g.521T>A showed statistically significant differences between groups (adjusted OR (95% CI): 0.15 (0.03–0.76), 𝑃 = 0.022; 5.76 (1.03–32.1), P = 0.046, respectively). It suggests that in the studied population the 𝐼𝐿1𝐴/1_g.388C allele is associated with a decreased PD risk, whereas the 𝐼𝐿1𝐴/1_g.521A allele can confer an increased risk. Additionally, the 𝐼𝐿1𝐴/2_g.515G>T variation resulted in a change of amino acid, i.e. glycine to valine. In silico analysis suggests that this change can alter protein structure and function, predicting it to be deleterious or damaging. This work suggests that 𝐼𝐿1 genetic variants may be important in PD susceptibility in canines.

• Frequency of congenital malformations and chromosomal disorders in Bacau and Vaslui counties (Romania)

This paper presents the state of genetic health of the human populations in two Romanian counties, Bacau and Vaslui, as they are different in area, number of inhabitants, level of economic and social development, etc. The data presented in this paper is from the Public Health Directions of the two counties, reflecting the situation recorded during 2006–2013. In the 8 years study, 1894 cases of congenital and chromosomal disorders were recorded in the newborns from the populations in the two counties. The identified cases were distributed based on years, categories of disorders and sexes. The average frequency of congenital disorders in the two populations over the investigated period was about 1.65 in Bacau county and 1.83% in Vaslui counties. In the population of Bacau county, these disorders affect in the same number in both the sexes (49.62% female cases and 50.38% male cases), while in Vaslui, the male cases are more than the females (53.92 and 46.08%, respectively). The main congenital disorders observed were: cardiovascular system anomalies, musculoskeletal system, urogenital system, etc. During the investigation period, in the human population of Bacau county, 97 cases of newborns with chromosomal disorders were diagnosed (0.16% of the living newborns), while in Vaslui county there were 106 cases (0.26% of the living newborns). Among these disorders, the Down’s syndrome was the most frequent one, representing 83.5 and 85.8% of cases in the population of Bacau county, and Vaslui counties.

• Microarray-based large scale detection of single feature polymorphism in Gossypium hirsutum L.

Microarrays offer an opportunity to explore the functional sequence polymorphism among different cultivars of many crop plants. The Affymetrix microarray expression data of five genotypes of Gossypium hirsutum L. at six different fibre developmental stages was used to identify single feature polymorphisms (SFPs). The background corrected and quantile-normalized log2 intensity values of all probes of triplicate data of each cotton variety were subjected to SFPs call by using SAM procedure in R language software. We detected a total of 37,473 SFPs among six pair genotype combinations of two superior (JKC777 and JKC725) and three inferior (JKC703, JKC737 and JKC783) using the expression data. The 224 SFPs covering 51 genes were randomly selected from the dataset of all six fibre developmental stages of JKC777 and JKC703 for validation by sequencing on a capillary sequencer. Of these 224 SFPs, 132 were found to be polymorphic and 92 monomorphic which indicate that the SFP prediction from the expression data in the present study confirmed a ∼ 58.92% of true SFPs. We further identified that most of the SFPs are associated with genes involved in fatty acid, flavonoid, auxin biosynthesis etc. indicating that these pathways significantly involved in fibre development.

• Mutational landscape of the human Y chromosome-linked genes and loci in patients with hypogonadism

Sex chromosome-related anomalies engender plethora of conditions leading to male infertility. Hypogonadotropic hypogonadism (HH) is a rare but well-known cause of male infertility. Present study was conducted to ascertain possible consensus on the alterations of the Y-linked genes and loci in males representing hypogonadism (H), which in turn culminate in reproductive dysfunction. A total of nineteen 46, XY males, clinically diagnosed with H (11 representative HH adults and eight prepubertal boys suspected of having HH) were included in the study. Sequence-tagged site screening, 𝑆𝑅𝑌 gene sequencing, fluorescence in situ hybridization mapping (FISH), copy number and relative expression studies by real-time PCR were conducted to uncover the altered status of the Y chromosome in the patients. The result showed random microdeletions within the 𝐴𝑍𝐹𝑎 (73%)/𝑏 (78%) and 𝑐(26%) regions. Sequencing of the 𝑆𝑅𝑌 gene showed nucleotide variations within and outside of the HMG box in four males (21%). FISH uncovered mosaicism for 𝑆𝑅𝑌, 𝐴𝑀𝐸𝐿𝑌, 𝐷𝐴𝑍 genes and DYZ1 arrays, structural rearrangement for 𝐴𝑀𝐸𝐿𝑌 (31%) and duplication of 𝐷𝐴𝑍 (57%) genes. Copy number variation for seven Y-linked genes (2–8 rounds of duplication), DYZ1 arrays (495–6201copies) and differential expression of 𝑆𝑅𝑌, 𝑈𝑇𝑌 and 𝑉𝐶𝑌 in the patients’ blood were observed. Present work demonstrates the organizational vulnerability of several Y-linked genes in H males. These results are envisaged to be useful during routine diagnosis of H patients.

• CD133 and BMI1 expressions and its prognostic role in primary glioblastoma

Glioblastoma is the most common malignant brain tumour, generated by bulk of malignant cancer stem cells, which express various stem cell factors like CD133, BMI1 and nestin. There are several studies which show the importance of CD133 in cancer, but the function and interaction with other major oncogenes and tumour suppressor genes is still not understood. This study aimed to analyse the expression of CD133 mRNA and its correlations with BMI1 protein expression and 𝑇𝑃53 mutations in newly diagnosed glioblastoma patients and its role in prognosis. Overexpression of 𝐶𝐷133 mRNA and BMI1 protein was found in 47.6 and 76.2% patients respectively and 𝑇𝑃53 mutations was seen in 57.1% of patients in our study. There was no correlation among 𝑇𝑃53 mutations and expressions of 𝐶𝐷133 and BMI1. We found that high level of BMI1 expression was favourable for the patient survival (P = 0.0075) and high 𝐶𝐷133 mRNA expression was unfavourable for the patient survival (𝑃 = 0.0226). 𝐶𝐷133 mRNA and BMI1 protein expression could independently predict the glioblastoma patient survival in multivariate analysis. In conclusion, the overexpression of these stem cell markers is a common event in glioblastoma progression and could be used as potential prognostic markers.

• Genetic diversity and population structure of endangered Aquilaria malaccensis revealed potential for future conservation

The endangered Aquilaria malaccensis, is an important plant with high economic values. Characterization of genetic diversity and population structure is receiving tremendous attention for effective conservation of genetic resources. Considering important repositories of biological diversity, the genetic relationships of 127 A. malaccensis accessions from 10 home gardens of three states of northeast India were assessed using amplified fragment length polymorphism (AFLP). Of the 1153 fragments amplified with four AFLP primer combinations, 916 (79.4%) were found to be polymorphic. Polymorphic information content (PIC) and marker index (MI) of each primer combination correlate significantly with the number of genotypes resolved. Overall, a high genetic diversity (avg. 71.85%) was recorded. Further, high gene flow (𝑁m : 3.37), low genetic differentiation (𝐹ST : 0.069) and high within population genetic variation (93%) suggests that most of the genetic diversity is restricted within population. Neighbour joining (NJ), principal coordinate analysis (PCoA) and Bayesian-based STRUCTURE grouped all the accessions in two clusters with significant intermixing between populations, therefore, revealed that two genetically distinct gene pools are operating in the A. malaccensis populations cultivated in home gardens. Based on the various diversity inferences, five diverse populations (JOH, FN, HLF, DHM and ITN) were identified, which can be potentially exploited to develop conservation strategies for A. malaccensis.

• Rapid cloning and bioinformatic analysis of spinach Y chromosome-specific EST sequences

The genome of spinach single chromosome complement is about 1000 Mbp, which is the model material to study the molecular mechanisms of plant sex differentiation. The cytological study showed that the biggest spinach chromosome (chromosome 1) was taken as spinach sex chromosome. It had three alleles of sex-related 𝑋, 𝑋m and 𝑌. Many researchers have been trying to clone the sex-determining genes and investigated the molecular mechanism of spinach sex differentiation. However, there are no successful cloned reports about these genes. A new technology combining chromosome microdissection with hybridization-specific amplification (HSA) was adopted. The spinach Y chromosome degenerate oligonucleotide primed-PCR (DOP-PCR) products were hybridized with cDNA of the male spinach flowers in florescence. The female spinach genome was taken as blocker and cDNA library specifically expressed in Y chromosome was constructed. Moreover, expressed sequence tag (EST) sequences in cDNA library were cloned, sequenced and bioinformatics was analysed. There were 63 valid EST sequences obtained in this study. The fragment size was between 53 and 486 bp. BLASTn homologous alignment indicated that 12 EST sequences had homologous sequences of nucleic acids, the rest were new sequences. BLASTx homologous alignment indicated that 16 EST sequences had homologous protein-encoding nucleic acid sequence. The spinach Y chromosome-specific EST sequences laid the foundation for cloning the functional genes, specifically expressed in spinach Y chromosome. Meanwhile, the establishment of the technology system in the research provided a reference for rapid cloning of other biological sex chromosome-specific EST sequences.

• Characterization of MTNR1A gene in terms of genetic variability in a panel of subtemperate and subtropical Indian sheep breeds

Seasonality of animals is an important adaptive trait for successful survival and production during limited food availability and extreme environmental conditions. Photoperiodic changes in day length are utilized by these seasonal animals as an important environmental cue for regulating their annual rhythms of reproduction cycles. Melatonin is an important hormone which is secreted by the pineal gland in proportion to darkness and its effect is mediated by melatonin receptor subtypes, principally 𝑀𝑇𝑁𝑅1𝐴. In the present study, polymorphism in the coding sequence at two important SNPs (C606T and G612A), known to be markers for out of season breeding in sheep were studied by PCR-RFLP in a panel of four breeds of sheep from subtemperate and subtropical arid conditions, respectively. The frequencies of G' and A' alleles with reference to G612A SNP did not differ considerably among all the breeds of sheep. Frequency of T' allele of the C606T SNP was found to be dominantly higher in subtemperate sheep breeds in comparison to subtropical sheep breeds. Identified SNPs in the coding region were mostly synonymous and did not lead to any change in conformation of the MTNR1A receptor protein.

• Development of molecular map and identification of QTLs linked to Fusarium wilt resistance in chickpea

A number of genetic maps for Fusarium wilt resistance in chickpea have been reported in earlier studies, however QTLs identified for Fusarium wilt resistance were unstable. Hence, the present study aims to map novel molecular markers and to identify QTLs for Fusarium wilt resistance in chickpea. An intraspecific linkage map of chickpea (Cicer arietinum L.) was constructed using F10–F11 recombinant inbred lines (RILs) derived from a cross between K850 and WR315 segregating for H2 locus. A set of 31 polymorphic simple sequence repeat (SSR) markers obtained by screening 300 SSRs and were used for genotyping. The linkage map had four linkage groups and coverage of 690 cM with a marker density of 5.72 cM. The RILs were screened for their wilt reaction across two seasons in wilt sick plot at International Crop Research Institute for Semi-Arid Tropics (ICRISAT), Hyderabad, India. Five major quantitative trait loci (QTLs) were detected in both seasons for late wilting (60 days after sowing). A stable QTL (GSSR 18-TC14801) for wilt resistance was identified in both the seasons, and the QTL explained a variance of 69.80 and 60.80% in 2007 and 2008 rabi respectively.

• Comparing genetic variants detected in the 1000 genomes project with SNPs determined by the International HapMap Consortium

Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide a means for assessing concerns regarding SNP array-based GWAS findings as well as for realistically bounding expectations for next generation sequencing (NGS)-based GWAS. We calculated and compared base composition, transitions to transversions ratio, minor allele frequency and heterozygous rate for SNPs from HapMap and 1KGP for the 622 common individuals. We analysed the genotype discordance between HapMap and 1KGP to assess consistency in the SNPs from the two references. In 1KGP, 90.58% of 36,817,799 SNPs detected were not measured in HapMap. More SNPs with minor allele frequencies less than 0.01 were found in 1KGP than HapMap. The two references have low discordance (generally smaller than 0.02) in genotypes of common SNPs, with most discordance from heterozygous SNPs. Our study demonstrated that SNP array-based GWAS findings were reliable and useful, although only a small portion of genetic variances were explained. NGS can detect not only common but also rare variants, supporting the expectation that NGS-based GWAS will be able to incorporate a much larger portion of genetic variance than SNP arrays-based GWAS.

• Identification and introgression of QTLs implicated in resistance to sorghum downy mildew (Peronosclerospora sorghi (Weston and Uppal) C. G. Shaw) in maize through marker-assisted selection

Sorghum downy mildew caused by Peronosclerospora sorghi is a major disease of maize and resistance is under the control of polygenes which necessitated identification of quantitative-trait loci (QTLs) for initiating marker-assisted introgression of resistant QTLs in elite susceptible inbred lines. In the present study, QTLs for sorghum downy mildew (SDM) resistance in maize were identified based on cosegregation with linked simple sequence repeats in 185 F2 progeny from a cross between susceptible (CM500-19) and resistant (MAI105) parents. F3 families were screened in the National Sorghum Downy Mildew Screening Nursery during 2010 and 2011. High heritability was observed for the disease reaction. The final map generated using 87 SSR markers had 10 linkage groups, spanning a length of 1210.3 cM. Although, we used only 87 SSR markers for mapping, the per cent of genome within 20 cM to the nearest marker was 88.5. Three putative QTLs for SDM resistance were located on chromosomes 3 (bin 3.01), 6 (bin 6.01) and 2 (bin 2.02) using composite interval mapping. The locus on chromosome 3 had a major effect and explained up to 12.6% of the phenotypic variation. The other two QTLs on chromosomes 6 and 2 had minor effects with phenotypic variation of 7.1 and 2%. The three QTLs appeared to have additive effects on resistance. The QTLs on chromosomes 3 and 6 were successfully used in the marker-assisted selection programme for introgression of resistance to SDM in eight susceptible maize lines.

• Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary multiple osteochondromas

• Whole exome sequencing reveals a 𝑀𝐿𝐿 de novo mutation associated with mild developmental delay and without `hairy elbows’: expanding the phenotype of Wiedemann–Steiner syndrome

• A note on the variance of the estimate of the fixation index F

• Characterization of drug-metabolizing enzymes CYP2C9, CYP2C19 polymorphisms in Tunisian, Kuwaiti and Bahraini populations

• LncRNAs: emerging players in gene regulation and disease pathogenesis

The advent of next-generation sequencing has demonstrated that eukaryotic genomes are extremely complex than what were previously thought. Recent studies revealed that in addition to protein-coding genes, nonprotein-coding genes have allocated a large fraction of the genome. Long noncoding RNA (lncRNA) genes are classified as nonprotein-coding genes, serving as a molecular signal, decoy, guide and scaffold. They were suggested to play important roles in chromatin states, epigenetic and posttranscriptional regulation of genes. Aberrant expression of lncRNAs and changes in their structure are associated with a wide spectrum of diseases ranging from different types of cancer and neurodegeneration to 𝛼-thalassaemia. The purpose of this study was to summarize the current progress in understanding the genomic bases and origin of lncRNAs. Moreover, this study focusses on the diverse functions of lncRNAs in normal cells as well as various types of disease to illustrate the potential impacts of lncRNAs on diverse biological processes and their therapeutic significance.

• Status of research on Drosophila ananassae at global level

Drosophila, a dipteran insect, has been found to be the best biological model for different kinds of studies. D. melanogaster was first described by Meigen in 1830, is most extensively studied species of the genus Drosophila and a number of investigations employing this species have been documented in areas such as genetics, behaviour, evolution, development, molecular biology, ecology, population biology, etc. Besides D. melanogaster, a number of other species of the genus Drosophila have also been used for different kinds of investigations. Among these, D. ananassae, a cosmopolitan and domestic species endowed with several unusual genetic features, is noteworthy. Described for the first time from Indonesia (Doleschall 1858), this species is commonly distributed in India. Extensive research work on D. ananassae has been done by numerous researchers pertaining to cytology, genetics, mutagenesis, gene mapping, crossing-over in both sexes, population and evolutionary genetics, behaviour genetics, ecological genetics, sexual isolation, fluctuating asymmetry, trade-offs etc. Genome of D. ananassae has also been sequenced. The status of research on D. ananassae at global level is briefly described in this review. Bibliography on this species from different countries worldwide reveals that maximum contribution is from India.

• Dynamics of sex expression and chromosome diversity in Cucurbitaceae: a story in the making

The family Cucurbitaceae showcases a wide range of sexual phenotypes being variedly regulated by biological and environmental factors. In the present context, we have tried to assemble reports of cytogenetic investigations carried out in cucurbits accompanied by information on sex expression diversities and chromosomal or molecular basis of sex determination in dioecious (or other sexual types, if reported) taxa known so far. Most of the Cucurbitaceae tribes have mixed sexual phenotypes with varying range of chromosome numbers and hence, ancestral conditions become difficult to probe. Occurrence of polyploidy is rare in the family and has no influence on sexual traits. The sex determination mechanisms have been elucidated in some well-studied taxa like Bryonia, Coccinia and Cucumis showing interplay of genic, biochemical, developmental and sometimes chromosomal determinants. Substantial knowledge about genic and molecular sex differentiation has been obtained for genera like Momordica, Cucurbita and Trichosanthes. The detailed information on sex determination schemes, genomic sequences and molecular phylogenetic relationships facilitate further comprehensive investigations in the tribe Bryonieae. The discovery of organ identity genes and sex-specific sequences regulating sexual behaviour in Coccinia, Cucumis and Cucurbita opens up opportunities of relevant investigations to answer yet unaddressed questions pertaining to floral unisexuality, dioecy and chromosome evolution in the family. The present discussion brings the genera in light, previously recognized under subfamily Nhandiroboideae, where the study of chromosome cytology and sex determination mechanisms can simplify our understanding of sex expression pathways and its phylogenetic impacts.

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