Actinidia chinensis(kiwifruit)is a perennial horticultural crop species of the Actinidiaceae family with high nutritional and economic value.Two versions of the A.chinensis genomes have been previously assembled,based...Actinidia chinensis(kiwifruit)is a perennial horticultural crop species of the Actinidiaceae family with high nutritional and economic value.Two versions of the A.chinensis genomes have been previously assembled,based mainly on relatively short reads.Here,we report an improved chromosome-level reference genome of A.chinensis(v3.0),based mainly on PacBio long reads and Hi-C data.The high-quality assembled genome is 653 Mb long,with 0.76%heterozygosity.At least 43%of the genome consists of repetitive sequences,and the most abundant long terminal repeats were further identified and account for 23.38%of our novel genome.It has clear improvements in contiguity,accuracy,and gene annotation over the two previous versions and contains 40,464 annotated protein-coding genes,of which 94.41%are functionally annotated.Moreover,further analyses of genetic collinearity revealed that the kiwifruit genome has undergone two whole-genome duplications:one affecting all Ericales families near the K-T extinction event and a recent genus-specific duplication.The reference genome presented here will be highly useful for further molecular elucidation of diverse traits and for the breeding of this horticultural crop,as well as evolutionary studies with related taxa.展开更多
Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research....Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research.The role of MNVs in genetic diagnosis remains inadequately characterized,particularly within large disease cohorts.In this study,we comprehensively investigate codon-level MNVs(cMNVs)across 157 hearing loss(HL)-related genes in 11,467 HL cases and 7258 controls from the Chinese Deafness Gene Consortium(CDGC)cohort.A total of 116 cMNVs are identified,occurring in 29.07%of HL cases.Among them,56.03%of cMNVs exhibit functional consequences distinct from constituent SNVs.Moreover,amino acid substitutions exclusive to cMNVs cause more substantial physicochemical disruptions than those associated with SNVs.Notably,51 cMNVs show pathogenicity classifications that diverge from at least one constituent SNV,impacting genetic interpretation in 145 cases.Pathogenicity interpretation of cMNV facilitates definitive genetic diagnoses in eight HL cases that would otherwise have been subject to misdiagnoses or missed diagnoses.These findings provide critical insights into the genomic characteristics,functional impacts,and diagnostic implications of cMNVs,underscoring their clinical significance in genetic diagnosis and emphasizing the necessity for comprehensive and accurate detection and interpretation of cMNVs in genetic testing and research.展开更多
基金supported by the National Key Research and Development Program of China(ref.2017YFC0505203)Fundamental Research Funds for the Central Universities(ref.2018CDDY-S02-SCU)+1 种基金National High-Level Talents Special Support Plan(10 Thousand Talents Plan)985 and 211 Projects of Sichuan University.
文摘Actinidia chinensis(kiwifruit)is a perennial horticultural crop species of the Actinidiaceae family with high nutritional and economic value.Two versions of the A.chinensis genomes have been previously assembled,based mainly on relatively short reads.Here,we report an improved chromosome-level reference genome of A.chinensis(v3.0),based mainly on PacBio long reads and Hi-C data.The high-quality assembled genome is 653 Mb long,with 0.76%heterozygosity.At least 43%of the genome consists of repetitive sequences,and the most abundant long terminal repeats were further identified and account for 23.38%of our novel genome.It has clear improvements in contiguity,accuracy,and gene annotation over the two previous versions and contains 40,464 annotated protein-coding genes,of which 94.41%are functionally annotated.Moreover,further analyses of genetic collinearity revealed that the kiwifruit genome has undergone two whole-genome duplications:one affecting all Ericales families near the K-T extinction event and a recent genus-specific duplication.The reference genome presented here will be highly useful for further molecular elucidation of diverse traits and for the breeding of this horticultural crop,as well as evolutionary studies with related taxa.
基金supported by the Key Project of the National Natural Science Foundation of China(82030030)the National Natural Science Foundation of China(82171836)+1 种基金the Science and Technology Department of Sichuan Province(2024NSFSC0648)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002).
文摘Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research.The role of MNVs in genetic diagnosis remains inadequately characterized,particularly within large disease cohorts.In this study,we comprehensively investigate codon-level MNVs(cMNVs)across 157 hearing loss(HL)-related genes in 11,467 HL cases and 7258 controls from the Chinese Deafness Gene Consortium(CDGC)cohort.A total of 116 cMNVs are identified,occurring in 29.07%of HL cases.Among them,56.03%of cMNVs exhibit functional consequences distinct from constituent SNVs.Moreover,amino acid substitutions exclusive to cMNVs cause more substantial physicochemical disruptions than those associated with SNVs.Notably,51 cMNVs show pathogenicity classifications that diverge from at least one constituent SNV,impacting genetic interpretation in 145 cases.Pathogenicity interpretation of cMNV facilitates definitive genetic diagnoses in eight HL cases that would otherwise have been subject to misdiagnoses or missed diagnoses.These findings provide critical insights into the genomic characteristics,functional impacts,and diagnostic implications of cMNVs,underscoring their clinical significance in genetic diagnosis and emphasizing the necessity for comprehensive and accurate detection and interpretation of cMNVs in genetic testing and research.
