•First study to see association of LEP-2548G/A, 19G/A and LEPR 668A/G with T2DM in North Indians.•LEP-2548G/A and LEPR 668A/G polymorphism showed association with T2DM.•LEP gene Haplotype A-G ...conferred 2.35 folds risk towards T2DM progression.•The genetic variants LEP −2548G/A and LEPR 668A/G are significantly associated with RBS and LDL-C levels.
Obesity is a major risk factor in aetiology of type 2 diabetes mellitus (T2DM). Leptin (LEP) is an anti-obesity hormone which regulates food intake, energy expenditure and glucose metabolism. The genetic variants in leptin and leptin receptor gene (LEPR) may play major role in the pathogenesis of T2DM and obesity. The current study aimed to investigate the association of polymorphisms in LEP (rs7799039, −2548G/A and rs2167270, 19G/A) and LEPR (rs1137101, 668A/G) gene with type 2 diabetes in North Indian Punjabi population.
A total of 817 subjects were included for the present case-control study, consisting of 417 T2DM patients and 400 healthy controls. The anthropometric, physiometric and biochemical measurements were taken from all the subjects. The genotyping of LEP and LEPR gene variants were carried out by polymerase chain reaction based restriction fragment length polymorphism method (PCR-RFLP), followed by genotyping of 10% of the samples for each polymorphism by Sanger sequencing method for quality control measurement.
The risk genotype frequencies were found to be significantly higher in T2DM cases than control subjects (rs7799039, p = 0.001; rs2167270, p = 0.019 and rs1137101, p = 0.003). Under recessive genetic model LEPrs7799039 and LEPRrs1137101 polymorphism conferred 3.4 and 2.1 fold risk towards the development of T2DM after adjustment of various covariates (OR = 3.44, 95%CI: 1.768–6.681, p = 0.001 and OR: 2.12, 95%CI: 1.256–3.569, p = 0.005, respectively). In the stratified analysis of LEP variant rs7799039 by age, gender, BMI and alcohol use, a significantly increased risk of T2DM was found in female, BMI ≥ 23 and never drinking subgroups. However, in the LEPR variant rs1137101, significantly increased risk of T2DM was observed in age <50, male, BMI ≥ 23 and never drinking subgroup. The A-G haplotype combination of rs7799039A and rs2167270G conferred significant 2 fold risk towards T2DM (OR = 2.35, 95%CI: 1.34–4.12, p = 0.002). In control group, the genetic variants rs7799039 and rs1137101 were significantly associated with levels of random blood sugar and low density lipoprotein cholesterol levels.
The present study revealed the association of LEP rs7799039 and LEPR rs1137101 with type 2 diabetes mellitus, which suggest its predominant role in the estimation of type 2 diabetes mellitus in North Indian Punjabi population.
INTRODUCTION
Sequence variants in TMEM106B have been associated with an increased risk of developing dementia.
METHODS
As part of our efforts to generate a set of mouse lines in which we replaced the ...mouse Tmem106b gene with a human TMEM106B gene comprised of either a risk or protective haplotype, we conducted an in‐depth sequence analysis of these alleles. We also analyzed transcribed TMEM106B sequences using RNA‐seq data (AD Knowledge portal) and full genome sequences (1000 Genomes).
RESULTS
We identified an AluYb8 insertion in the 3' untranslated region (3'UTR) of the TMEM106B risk haplotype. We found this AluYb8 insertion in every risk haplotype analyzed, but not in either protective haplotypes or in non‐human primates.
DISCUSSION
We conclude that this risk haplotype arose early in human development with a single Alu‐insertion event within a unique haplotype context. This AluYb8 element may act as a functional variant in conferring an increased risk of developing dementia.
Highlights
We conducted an in‐depth sequence analysis of (1) a risk and (2) a protective haplotype of the human TMEM106B gene.
We also analyzed transcribed TMEM106B sequences using RNA‐seq data (AD Knowledge Portal) and full genome sequences (1000 Genomes).
We identified an AluYb8 insertion in the 3' untranslated region (3'UTR) of the TMEM106B risk haplotype. We found this AluYb8 insertion in every risk haplotype analyzed, but not in either protective haplotypes or in non‐human primates.
This AluYb8 element may act as a functional variant in conferring an increased risk of developing dementia.
Early season flooding is a major constraint in direct-seeded rice, as rice genotypes vary in their coleoptile length during anoxia.
(
,
) has been identified as the genetic determinant for anaerobic ...germination (AG) and coleoptile elongation during flooding. We evaluated the coleoptile length of a diverse rice panel under normal and flooded conditions and investigated the Korean rice collection of 475 accessions to understand its genetic variation, population genetics, evolutionary relationships, and haplotypes in the
gene. Most accessions displayed enhanced flooded coleoptile lengths, with the temperate
ecotype exhibiting the highest average values for normal and flooded conditions. Positive Tajima's D values in
, admixture, and tropical
ecotypes suggested balancing selection or population expansion. Haplotype analysis revealed 18 haplotypes, with three in cultivated accessions, 13 in the wild type, and two in both. Hap_1 was found mostly in
, while Hap-2 and Hap_3 were more prevalent in
accessions. Further phenotypic performance of major haplotypes showed significant differences in flooded coleoptile length, flooding tolerance index, and shoot length between Hap_1 and Hap_2/3. These findings could be valuable for future selective rice breeding and the development of efficient haplotype-based breeding strategies for improving flood tolerance.
Fast-forward breeding for a food-secure world Varshney, Rajeev K.; Bohra, Abhishek; Roorkiwal, Manish ...
Trends in genetics,
December 2021, 2021-12-00, 20211201, Letnik:
37, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Crop production systems need to expand their outputs sustainably to feed a burgeoning human population. Advances in genome sequencing technologies combined with efficient trait mapping procedures ...accelerate the availability of beneficial alleles for breeding and research. Enhanced interoperability between different omics and phenotyping platforms, leveraged by evolving machine learning tools, will help provide mechanistic explanations for complex plant traits. Targeted and rapid assembly of beneficial alleles using optimized breeding strategies and precise genome editing techniques could deliver ideal crops for the future. Realizing desired productivity gains in the field is imperative for securing an adequate future food supply for 10 billion people.
The rapid advances in plant genome sequencing and phenotyping have enhanced trait mapping and gene discovery in crops.Increasing adoption of machine learning algorithms is crucial to derive meaningful inferences from complex multidimensional phenotyping data.Emerging breeding approaches like optimal contribution selection, alone or in combination with genomic selection, will enhance the genetic base of breeding programs while accelerating genetic gain.Integrating speed breeding with new-age genomic breeding technologies holds promise to relieve the long-standing bottleneck of lengthy crop breeding cycles.Haplotype-based breeding, genomic prediction, and genome editing will hasten targeted assembly of superior alleles in future cultivars for sustainable agricultural development and long-term food security.
The C9orf72 hexanucleotide repeat expansion (HRE) is a common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The inheritance is autosomal dominant, but a high ...proportion of subjects with the mutation are simplex cases. One possible explanation is de novo expansions of unstable intermediate-length alleles (IAs). Using haplotype sharing trees (HSTs) with the haplotype analysis tool kit (HAPTK), we derived majority-based ancestral haplotypes of HRE samples and discovered that IAs containing ≥18–20 repeats share large haplotypes in common with the HRE. Using HSTs of HRE and IA samples, we demonstrate that the longer IA haplotypes are largely indistinguishable from HRE haplotypes and that several ≥18–20 IA haplotypes share over 5 Mb (>600 markers) haplotypes in common with the HRE haplotypes. These analysis tools allow physical understanding of the haplotype blocks shared with the majority-based ancestral haplotype. Our results demonstrate that the haplotypes with longer IAs belong to the same pool of haplotypes as the HRE and suggest that longer IAs represent potential premutation alleles.
Using haplotype sharing trees and majority-based ancestral haplotypes, we demonstrate that the C9orf72 hexanucleotide repeat expansion and alleles with ≥18–20 repeats share large haplotype blocks, indicating very recent shared ancestry. This was in sharp contrast to the shorter alleles, suggesting that expansions might be formed from the longer repeat alleles.
The HLA-G (human leukocyte antigen-G) molecule plays a pivotal role in immune tolerance by inhibiting different cell subsets involved in both innate and adaptive immunity. Besides its primary ...function in maintaining the maternal-fetal tolerance, HLA-G has been involved in a wide range of pathological conditions where it can be either favorable or detrimental to the patient, depending on the nature of the pathology. Although several studies have demonstrated the utmost importance of the 3' untranslated region (3'UTR) in the HLA-G expression profile, limited data exist on the sequence variability of this gene region in human populations. In this study, we characterized the genetic diversity and haplotype structure of the HLA-G 3'UTR by resequencing 444 individuals from three sub-Saharan African populations and retrieving data from the 1000 Genomes project and the literature. A total of 1936 individuals representing 21 worldwide populations were combined and jointly analyzed. Our data revealed a high level of nucleotide diversity, an excess of intermediate frequency variants and an extremely low population differentiation, strongly supporting a history of balancing selection at this locus. The 14-bp insertion/deletion polymorphism was further pointed out as the likely target of selection, emphasizing its potential role in the post-transcriptional regulation of HLA-G expression.
Obesity and its effects on increasing morbidity and mortality have reached the level of an epidemic with a high frequency in modern populations. IL-6 released from adipose tissue is known to trigger ...the chronic inflammation in obesity. CXCL5, which mediates the activation and migration of neutrophils, has been found at high levels in obese subjects. In our study, we aimed to investigate the possible effects of IL-6, IL-6R and CXCL5, polymorphisms and haplotypes on the development of obesity. We studied IL-6, rs2069827 (-1363, G/T), rs1800797 (-597, G/A), rs1800796 (-572, G/C) and rs1800795 (-174, G/C), IL-6R rs4845617 (-183, G/A), rs2228145 (+48892, A/C) and CXCL5 rs352046 (-156, G/C) polymorphic sites in 60 obesity patients and 59 healthy controls. For genotyping we used PCR-RFLP based approach. The IL-6 rs1800796, rs1800795 and IL-6R rs4845617 G allelles could be the possible genetic factors responsible for obesity. We found similar results in female obese group. The results indicated that there was no association between obesity and other SNPs (rs2069827, rs1800797, and rs1800795 and rs2228145) and CXCL5, rs352046. The results of IL-6 and IL-6R haplotype analysis by global differentiation test showed that haplotypes may have different distributions between obese and controls. Our results showed that polymorphisms and possible haplotypes in IL-6 and IL-6R genes, which have an important role in inflammation, may affect the development of obesity. This study points out the necessity of investigating the possible effects of gene polymorphisms of other cytokines and their receptors in the development of obesity in larger populations.
B2 haplotype major histocompatibility complex (MHC) has been extensively reported to confer resistance to various avian diseases. But its peptide-binding motif is unknown, and the presenting peptide ...is rarely identified. Here, we identified its peptide-binding motif (X-A/V/I/L/P/S/G-X-X-X-X-X-X-V/I/L) in vitro using Random Peptide Library-based MHC I LC-MS/MS analysis. To further clarify the structure basis of motif, we determined the crystal structure of the BF2∗02:01-PB2552-560 complex at 1.9 Å resolution. We found that BF2∗02:01 had a relatively wide antigen-binding groove, and the structural characterization of pockets was consistent with the characterization of peptide-binding motif. The wider features of the peptide-binding motif and increased number of peptides bound by BF2∗02:01 than BF2∗04:01 might resolve the puzzles for the presence of potential H9N2 resistance in B2 chickens. Afterward, we explored the H9N2 avian influenza virus (AIV)-induced cellular immune response in B2 haplotype chickens in vivo. We found that ratio of CD8+ T cell and kinetic expression of cytotoxicity genes including Granzyme K, interferon-γ, NK lysin, and poly-(ADP-ribose) polymerase in peripheral blood mononuclear cells were significantly increased in defending against H9N2 AIV infection. Especially, we selected 425 epitopes as candidate epitopes based on the peptide-binding motif and further identified four CD8+ T-cell epitopes on H9N2 AIV including NS198-106, PB2552-560, NP182-190, and NP455-463 via ELI-spot interferon-γ detections after stimulating memory lymphocytes with peptides. More importantly, these epitopes were found to be conserved in H7N9 AIV and H9N2 AIV. These findings provide direction for developing effective T cell epitope vaccines using well-conserved internal viral antigens in chickens.
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