Annals of Human Genetics最新文献

{"title":"Expression analysis of NF1-mutated alleles in a rare compound heterozygous spinal NF1 patient by digital PCR","authors":"Paola Bettinaglio,&nbsp;Viviana Tritto,&nbsp;Rosina Paterra,&nbsp;Marica Eoli,&nbsp;Paola Riva","doi":"10.1111/ahg.12540","DOIUrl":"10.1111/ahg.12540","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgroud</h3>\u0000 \u0000 <p>Neurofibromatosis type 1 (NF1) is a heterogeneous neurocutaneous disorder. Spinal neurofibromatosis (SNF) is a distinct clinical entity of NF1, characterized by bilateral neurofibromas involving all spinal nerve roots. Although both forms are caused by intragenic heterozygous variants of <i>NF1</i>, missense variants have been associated with SNF, according to a dominant inheritance model causing haploinsufficiency. Most patients carry pathogenic variants in one of the <i>NF1</i> alleles; nevertheless, patients with both <i>NF1</i>-mutated copies have been described. Interestingly, all <i>NF1</i> variants carried by the known SNF compound heterozygotes were missense/splicing variants or in-frame insertion-deletions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate whether there is a differential expression of <i>NF1</i> variant alleles in an <i>NF1</i> compound heterozygous SNF patient possibly contributing to clinical phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; methods</h3>\u0000 \u0000 <p>We performed an allele-specific expression study, by chip-based digital PCR, in an SNF family carrying two <i>NF1</i> missense variants. We evaluated the expression levels of the two <i>NF1</i>-mutated alleles both carried by the compound heterozygous SNF patient and his relatives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both alleles were expressed at comparable levels in the patient and hyper-expressed compared to the wild-type alleles of healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Here we provide new insights into expression studies of <i>NF1</i>-mutated transcripts suggesting that a novel pathogenetic mechanism, caused by gain-of-function variants, could be associated with SNF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Further studies should be performed in larger cohorts, opening new perspectives in the NF1 pathogenesis comprehension.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 3","pages":"183-193"},"PeriodicalIF":1.9,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138450769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cilia function and dysfunction","authors":"Kathryn E. Hentges,&nbsp;Colin A. Johnson","doi":"10.1111/ahg.12541","DOIUrl":"10.1111/ahg.12541","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 1","pages":"1-3"},"PeriodicalIF":1.9,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prevalence and linkage disequilibrium of 21 genetic variations related to thrombophilia, folate cycle, and hypertension in reproductive age women of Rostov region (Russia)","authors":"Oksana Yurievna Bordaeva,&nbsp;Ekaterina Grigorievna Derevyanchuk,&nbsp;Dema Alset,&nbsp;Maria Aleksandrovna Amelina,&nbsp;Tatiana Pavlovna Shkurat","doi":"10.1111/ahg.12539","DOIUrl":"10.1111/ahg.12539","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Several maternal genetic variations are known to play an important role during pregnancy since they can affect mother health and/or fetal growth. The frequency of these variants is variable among different populations. This study aimed to investigate thrombophilia, folate metabolism and hypertension genetic variants in reproductive age women of Rostov region (Russia) and then assess their linkage disequilibrium (LD) and heterogeneity among populations. A total of 3108 reproductive age women were included (33.75 ± 5.13 years). Twenty-one genetic variants were detected with RT-PCR. LD was tested according to (D′) coefficient and <i>p</i> value. The highest frequency of mutant allele in studied population was as follows: <i>PAI-1</i> rs1799768, <i>MTRR</i> rs1801394, <i>AGT</i> rs699, and <i>AGTR2</i> rs1403543. We showed a high possibility of coinheritance of <i>MTHFR</i> rs1801133 with rs1801131 and <i>AGT</i> rs699 with rs4762 (D′=0.992 and 0.999, respectively). In addition, comparative analysis showed <i>F7</i> rs6046, <i>FGB</i> rs1800790, <i>MTR</i> rs1805087, and <i>AGT</i> rs699 significantly more frequent among Rostov females by 1.3–1.5 times than European. <i>MTHFR</i> rs1801133, <i>ADD1</i> rs4961, <i>AGTR2</i> rs1403543, <i>NOS3</i> rs2070744, and rs1799983 were with higher frequencies in Europeans than those in the studied group. Our data could be used as a reference for further associative studies of targeted genetic variations in different pregnancy complications specifically in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 2","pages":"171-181"},"PeriodicalIF":1.9,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of TRIM5 variants on the susceptibility to HIV-1 infection and disease progression in the Polish population","authors":"Jolanta Bratosiewicz-Wąsik,&nbsp;Maria Miklasińska-Majdanik,&nbsp;Tomasz J. Wąsik","doi":"10.1111/ahg.12536","DOIUrl":"10.1111/ahg.12536","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgroud</h3>\u0000 \u0000 <p>Tripartite motif containing 5α protein is a factor contributing to intracellular defense mechanisms against human immunodeficiency virus-1 (HIV-1) infection. The studies of <i>TRIM</i>5 variants effects on the risk of HIV-1 infection and the clinical course of disease provided inconclusive results in different ethnic groups. The aim of this study was to investigate the influence of <i>TRIM</i>5 variants on susceptibility to HIV-1 infection and clinical parameters among Polish HIV-1-infected patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>In our study, we investigated 301 HIV-1-infected patients and 186 age-matched seronegative controls. Seven variants of the <i>TRIM</i>5 gene (rs7127617, rs3824949, rs3740996, rs11601507, rs10838525, rs11038628, and rs28381981) were genotyped using both sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>The frequencies of rs7127617 TT genotype and T allele occurrence were lower in HIV-1-infected subjects compared to controls (0.14 vs. 0.26 for T/T genotype and 0.45 vs. 0.54 for T allele), suggesting their possible protective effect (<i>p</i> = 0.005 and <i>p</i> = 0.007, respectively). Heterozygosity and presence of the T allele at rs3740996 were enriched in controls compared to HIV-1-infected group (0.19 vs. 0.12 for C/T genotype and 0.11 vs. 0.07 for T allele; <i>p</i> = 0.03 and <i>p</i> = 0.02, respectively). Moreover, rs3824949 CC genotype carriers had a lower viral load than patients bearing rs3824949 GG/CG genotypes (4.0 vs. 4.6 log copies/mL; <i>p</i> = 0.049); however, none of the variants affected CD4⁺ cell count. In conclusion, our data confirm the role of <i>TRIM</i>5 variants in the HIV-1 transmission and the clinical course of HIV-1 infection. The presence of rs7127617 TT genotype and T allele seems to protect against HIV-1 transmission in examined population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 2","pages":"154-170"},"PeriodicalIF":1.9,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive meta-analysis to identify susceptibility genetic variants for precocious puberty","authors":"Xiuli Gu,&nbsp;Weining Xiong,&nbsp;Yan Yang,&nbsp;Honggang Li,&nbsp;Chengliang Xiong","doi":"10.1111/ahg.12525","DOIUrl":"10.1111/ahg.12525","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Currently, several genetic variants in <i>ERα</i> gene (rs2234693 and rs9340799), <i>ERβ</i> gene (rs1256049 and rs4986938), <i>KISS1</i> gene (rs4889, rs1132506 and rs5780218), <i>LIN28B</i> gene (rs314263, rs314276 and rs314280), and <i>MKRN3</i> gene (rs2239669) have been repeatedly explored for their contribution to precocious puberty (PP) susceptibility. However, the results remain conflicting rather than conclusive. We here performed a meta-analysis to identify the real susceptibility genetic variants for PP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>After screening by inclusion criteria, 20 related studies were finally included in this meta-analysis. The odds ratios and 95% confidence intervals were calculated to assess the strength of association. Sensitive analysis, publication bias, and trial sequential analysis (TSA) were performed to evaluate the stability and reliability of results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Rs2234693, rs9340799, and rs1256049 were significantly associated with PP susceptibility (<i>p</i> &lt; 0.0084). Stratified analysis according to ethnicity showed that rs2234693 and rs9340799 were significantly associated with PP susceptibility in Asian and Chinese populations. Stratified analysis according to PP subtype showed that rs2234693 and rs9340799 were significantly associated with idiopathic central PP susceptibility in Asian and Chinese populations (<i>p</i> &lt; 0.0084). The results of publication bias, sensitivity analysis, and TSA provided solid evidence for the association between these three variants and PP susceptibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Rs2234693 and rs9340799 in <i>ERα</i> gene and rs1256049 in <i>ERβ</i> gene may serve as susceptive factors for PP development. The present finding should be confirmed in replication studies and reinforced in functional studies, which will ultimately improve the feasibility of the application of these three PP-susceptible loci in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 2","pages":"138-153"},"PeriodicalIF":1.9,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic variability in Joubert syndrome is partially explained by ciliary pathophysiology","authors":"Joshua w. Owens,&nbsp;Robert J. Hopkin,&nbsp;Lisa J. Martin,&nbsp;Andrew Kodani,&nbsp;Brittany N. Simpson","doi":"10.1111/ahg.12537","DOIUrl":"10.1111/ahg.12537","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p><b>Introduction</b>: Joubert syndrome (JS) arises from defects of primary cilia resulting in potential malformations of the brain, kidneys, eyes, liver, and limbs. Several of the 35+ genes associated with JS have recognized genotype/phenotype correlations, but most genes have not had enough reported individuals to draw meaningful conclusions.</p>\u0000 \u0000 <p><b>Methods</b>: A PubMed literature review identified 688 individuals with JS across 32 genes and 112 publications to bolster known genotype/phenotype relationships and identify new correlations.</p>\u0000 \u0000 <p>All included patients had the “molar tooth sign” and a confirmed genetic diagnosis. Individuals were categorized by age, ethnicity, sex and the presence of developmental disability/intellectual disability, hypotonia, abnormal eye movements, ataxia, visual impairment, renal impairment, polydactyly, and liver abnormalities.</p>\u0000 \u0000 <p><b>Results</b>: Most genes demonstrated unique phenotypic profiles. Grouping proteins based on physiologic interactions established stronger phenotypic relationships that reflect known ciliary pathophysiology. Age-stratified data demonstrated that end-organ disease is progressive in JS. Most genes demonstrated a significant skew towards having variants with either residual protein function or no residual protein function.</p>\u0000 \u0000 <p><b>Conclusion</b>: This cohort demonstrates that clinically meaningful genotype/phenotype relationships exist within most JS-related genes and can be referenced to allow for more personalized clinical care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 1","pages":"86-100"},"PeriodicalIF":1.9,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular structure and function of fibrocystin, the key gene product implicated in autosomal recessive polycystic kidney disease (ARPKD)","authors":"Travis A K Bannell,&nbsp;Joseph J B Cockburn","doi":"10.1111/ahg.12535","DOIUrl":"10.1111/ahg.12535","url":null,"abstract":"<p>Autosomal recessive polycystic kidney disease is an early onset inherited hepatorenal disorder affecting around 1 in 20,000 births with no approved specific therapies. The disease is almost always caused by variations in the polycystic kidney and hepatic disease 1 gene, which encodes fibrocystin (FC), a very large, single-pass transmembrane glycoprotein found in primary cilia, urine and urinary exosomes. By comparison to proteins involved in autosomal dominant PKD, our structural and molecular understanding of FC has lagged far behind such that there are no published experimentally determined structures of any part of the protein. Bioinformatics analyses predict that the ectodomain contains a long chain of immunoglobulin-like plexin-transcription factor domains, a protective antigen 14 domain, a tandem G8-TMEM2 homology region and a sperm protein, enterokinase and agrin domain. Here we review current knowledge on the molecular function of the protein from a structural perspective.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 1","pages":"58-75"},"PeriodicalIF":1.9,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functions of cilia in cardiac development and disease","authors":"Wasay Mohiuddin Shaikh Qureshi,&nbsp;Kathryn E. Hentges","doi":"10.1111/ahg.12534","DOIUrl":"10.1111/ahg.12534","url":null,"abstract":"<p>Errors in embryonic cardiac development are a leading cause of congenital heart defects (CHDs), including morphological abnormalities of the heart that are often detected after birth. In the past few decades, an emerging role for cilia in the pathogenesis of CHD has been identified, but this topic still largely remains an unexplored area. Mouse forward genetic screens and whole exome sequencing analysis of CHD patients have identified enrichment for <i>de novo</i> mutations in ciliary genes or non-ciliary genes, which regulate cilia-related pathways, linking cilia function to aberrant cardiac development. Key events in cardiac morphogenesis, including left–right asymmetric development of the heart, are dependent upon cilia function. Cilia dysfunction during left–right axis formation contributes to CHD as evidenced by the substantial proportion of heterotaxy patients displaying complex CHD. Cilia-transduced signaling also regulates later events during heart development such as cardiac valve formation, outflow tract septation, ventricle development, and atrioventricular septa formation. In this review, we summarize the role of motile and non-motile (primary cilia) in cardiac asymmetry establishment and later events during heart development.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 1","pages":"4-26"},"PeriodicalIF":1.9,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An indel introduced by Neanderthal introgression, rs3835124:ATTTATT > ATT, might contribute to prostate cancer risk by regulating PDK1 expression","authors":"Ying Chen,&nbsp;Xin-Yi Yu,&nbsp;Shuang-Jia Xu,&nbsp;Xiao-Qian Shi,&nbsp;Xin-Xin Zhang,&nbsp;Chang Sun","doi":"10.1111/ahg.12533","DOIUrl":"10.1111/ahg.12533","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Prostate cancer is one of the most common cancer types in males and rs12621278:A &gt; G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A &gt; G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Population genetics analysis and functional genomics work was performed for this locus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G &gt; A, rs139972066:AAAAAAAA &gt; AAAAAAAAA, and rs3835124:ATTTATT &gt; ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA &gt; AAAAAAAAA and rs116108611:G &gt; A are not able to alter <i>ITGA</i>6 (integrin alpha 6) and <i>ITGA</i>6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT &gt; ATT can significantly influence <i>PDK1</i> (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower <i>PDK1</i> expression and further different energy homeostasis from modern human.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provided new insight into the contribution of Neanderthal introgression to human phenotypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 2","pages":"126-137"},"PeriodicalIF":1.9,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-pass whole genome sequencing is a reliable and cost-effective approach for copy number variant analysis in the clinical setting","authors":"Patricia C. Mazzonetto,&nbsp;Darine Villela,&nbsp;Silvia Souza da Costa,&nbsp;Ana C. V. Krepischi,&nbsp;Fernanda Milanezi,&nbsp;Michele P. Migliavacca,&nbsp;Paulo M. Pierry,&nbsp;Adriano Bonaldi,&nbsp;Luiz Gustavo D. Almeida,&nbsp;Camila Alves De Souza,&nbsp;José Eduardo Kroll,&nbsp;Marcelo G. Paula,&nbsp;Rodrigo Guarischi-Sousa,&nbsp;Cristovam Scapulatempo-Neto,&nbsp;Carla Rosenberg","doi":"10.1111/ahg.12532","DOIUrl":"10.1111/ahg.12532","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Next generation sequencing technology has greatly reduced the cost and time required for sequencing a genome. An approach that is rapidly being adopted as an alternative method for CNV analysis is the low-pass whole genome sequencing (LP-WGS). Here, we evaluated the performance of LP-WGS to detect copy number variants (CNVs) in clinical cytogenetics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>DNA samples with known CNVs detected by chromosomal microarray analyses (CMA) were selected for comparison and used as positive controls; our panel included 44 DNA samples (12 prenatal and 32 postnatal), comprising a total of 55 chromosome imbalances. The selected cases were chosen to provide a wide range of clinically relevant CNVs, the vast majority being associated with intellectual disability or recognizable syndromes. The chromosome imbalances ranged in size from 75 kb to 90.3 Mb, including aneuploidies and two cases of mosaicism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All CNVs were successfully detected by LP-WGS, showing a high level of consistency and robust performance of the sequencing method. Notably, the size of chromosome imbalances detected by CMA and LP-WGS were compatible between the two different platforms, which indicates that the resolution and sensitivity of the LP-WGS approach are at least similar to those provided by CMA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Our data show the potential use of LP-WGS to detect CNVs in clinical diagnosis and confirm the method as an alternative for chromosome imbalances detection. The diagnostic effectiveness and feasibility of LP-WGS, in this technical validation study, were evidenced by a clinically representative dataset of CNVs that allowed a systematic assessment of the detection power and the accuracy of the sequencing approach. Further, since the software used in this study is commercially available, the method can easily be tested and implemented in a routine diagnostic setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 2","pages":"113-125"},"PeriodicalIF":1.9,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41109014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}