Whole exome sequencing identifies the novel putative gene variants related with type 2 diabetes in Mizo population, northeast India

Lalrohlui, Freda; Zohmingthanga, John; hruaii, Vanlal; Vanlallawma, Andrew; Kumar, Nachimuthu Senthil

doi:10.1016/j.gene.2020.145229

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…The strong and arguably misguided assumption that most genomic analyses make about the correctness of the reference genome has led to spurious clinical findings and mistaken disease associations. For example, a few previous clinical exome studies have erroneously implicated PSVs of missing paralogs of GRCh38 collapsed duplications, such as KCNJ18 and GPRIN2 , as contributing to diseases [59–62]. Here, we resolve variation in these regions and show that the T2T-CHM13 reference genome universally improves genomic analyses for all populations by correcting major structural defects and adding sequences that were absent from GRCh38.…”

Section: Discussionmentioning

confidence: 81%

A complete reference genome improves analysis of human genetic variation

Aganezov

Yan

Soto

et al. 2021

Preprint

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Compared to its predecessors, the Telomere-to-Telomere CHM13 genome adds nearly 200 Mbp of sequence, corrects thousands of structural errors, and unlocks the most complex regions of the human genome to clinical and functional study. Here we demonstrate how the new reference universally improves read mapping and variant calling for 3,202 and 17 globally diverse samples sequenced with short and long reads, respectively. We identify hundreds of thousands of novel variants per sample - a new frontier for evolutionary and biomedical discovery. Simultaneously, the new reference eliminates tens of thousands of spurious variants per sample, including up to a 12-fold reduction of false positives in 269 medically relevant genes. The vast improvement in variant discovery coupled with population and functional genomic resources position T2T-CHM13 to replace GRCh38 as the prevailing reference for human genetics.

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Section: Discussionmentioning

confidence: 81%

A complete reference genome improves analysis of human genetic variation

Aganezov

Yan

Soto

et al. 2021

Preprint

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“…YTHDC2 was found to be markedly downregulated in obese mice and its overexpression improved the liver steatosis and insulin resistance through binding to the mRNA of lipogenic genes (Zhou et al 2020). In addition, the whole exome sequencing has identified a variant of YTHDC2 which may contribute to type 2 diabetes susceptibility in Northeast India (Lalrohlui et al 2020). Until now, the expression and roles of m6A methylation regulatory factors mentioned above in DN are unknown.…”

Section: Discussionmentioning

confidence: 99%

METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of α-klotho

Deng

2021

Mol Med

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Background N6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. However, its functions in diabetic nephropathy (DN) have not been determined. Here, we investigated the role of METTL14, a key component of the m6A methyltransferase complex, in DN. Methods The expression of METTL14 was detected in DN patients and human renal glomerular endothelial cells (HRGECs). In vitro and in vivo experiments were performed to explore the functions of METTL14 on high glocse-induced HRGECs and renal injury of DN mice. We also investigated whether METTL14 works by regulating α-klotho expression through m6A modification. Results METTL14 were highly expressed in kidneys of DN patients and high glocse-induced HRGECs both at the mRNA and protein level. Overexpression of METTL14 increased ROS, TNF-α and IL-6 levels and apoptosis in HRGECs. Conversely, METTL14 silence decreased the levels of ROS, TNF-α and IL-6 and cell apoptosis. We confirmed that METTL14 down-regulated α-klotho expression in an m6A-dependent manner. In addition, we also found that METTL14 aggravated renal injury and inflammation of db/db mice, which could partially rescued by α-klotho. Conclusion Our data revealed that METTL14 plays a vital role in high glucose-induced glomerular endothelial cells and diabetic nephropathy through m6A modification of α-klotho.

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“…Notable examples encompass APC, AKT1 , and CDH1 in Gastric Cancer, KRT18, CYP4A11, SLC4A3, SLC26A5, KCNS1, ABCD1, YTHDC2, PINX1, TNRC6A, TACO1, LAMA1, ACP7 and ACP7 in Type 2 Diabetes, as well as MT-ND2, MT-ND6, NOTCH1 and FLT3 in Pediatric Leukaemia patients from Mizoram. 20 , 21 , 22 , 23 , 24 , 25 These genetic deviations may owe their existence to the distinctive attributes of the population, potentially serving as pivotal research entry points for exploring potential predisposition mechanisms. As an illustration, the DPYD gene encodes DPD, a determinant governing the bioavailability of 5-Fluorouracil, thus determining treatment efficacy and toxicity for solid tumour patients.…”

Section: Discussionmentioning

confidence: 99%

Cancer awareness, diagnosis and treatment needs in Mizoram, India: evidence from 18 years trends (2003–2020)

Zomawia,

Zami,

Vanlallawma

et al. 2023

The Lancet Regional Health - Southeast Asia

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Whole exome sequencing identifies the novel putative gene variants related with type 2 diabetes in Mizo population, northeast India

Cited by 5 publications

References 33 publications

A complete reference genome improves analysis of human genetic variation

A complete reference genome improves analysis of human genetic variation

METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of α-klotho

Cancer awareness, diagnosis and treatment needs in Mizoram, India: evidence from 18 years trends (2003–2020)

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