Annals of Human Genetics最新文献

{"title":"The expression of NOTUM in replantation of severed fingers may be an important treatment factor","authors":"Bin Li,&nbsp;Libing Xiao,&nbsp;Danhong Ye,&nbsp;Siyi Zhong,&nbsp;Qiaoyu Yan","doi":"10.1111/ahg.12487","DOIUrl":"10.1111/ahg.12487","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>After years of development, digital replantation has become a mature treatment. Although the <i>NOTUM</i> gene has been shown to be involved in the formation of vertebrate nerves, whether it contributes to the osteogenic mechanism of severed finger replantation remains unknown. In response to this, this study investigates the specific details of <i>NOTUM</i> involvement in replantation of severed fingers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The experimental subjects are patients with replantation of severed fingers from Shulan International Medical College of Shulan (Hangzhou) Hospital affiliated to Zhejiang Shuren University. In addition to using bone marrow mesenchymal stem cells (BMSCs) as an in vitro system, this experiment also involves quantitative polymerase chain reaction, microarray analysis, cell counting Kit-8, ethynyl deoxyuridine staining and Western blot analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression level of NOTUM in the severed finger replantation group is lower than that in the normal group. NOTUM inhibits cell growth and cell transfer, osteogenic differentiation and β-catenin gene expression in BMSCs. Luciferase reporter assay illustrated that β-catenin wild type closely correlated with NOTUM. The inhibition of β-catenin increases the effects of <i>NOTUM</i> on cell growth, cell transfer and osteogenic differentiation of BMSCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Considering that <i>NOTUM</i> can inhibit cell growth, cell transfer, osteogenic differentiation of BMSCs, as well as the gene expression of β-catenin, it may be a biomarker of osteogenic differentiation and a potential therapeutic target for replantation of severed fingers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 1-2","pages":"18-27"},"PeriodicalIF":1.9,"publicationDate":"2022-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10867517","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":"Proteome changes in autosomal recessive primary microcephaly","authors":"Sami Zaqout,&nbsp;Atef Mannaa,&nbsp;Oliver Klein,&nbsp;Angelika Krajewski,&nbsp;Joachim Klose,&nbsp;Lena Luise-Becker,&nbsp;Ahmed Elsabagh,&nbsp;Khaled Ferih,&nbsp;Nadine Kraemer,&nbsp;Ethiraj Ravindran,&nbsp;Konstantin Makridis,&nbsp;Angela M. Kaindl","doi":"10.1111/ahg.12489","DOIUrl":"10.1111/ahg.12489","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/aim</h3>\u0000 \u0000 <p>: Autosomal recessive primary microcephaly (MCPH) is a rare and genetically heterogeneous group of disorders characterized by intellectual disability and microcephaly at birth, classically without further organ involvement. MCPH3 is caused by biallelic variants in the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 gene <i>CDK5RAP2</i>. In the corresponding <i>Cdk5rap2</i> mutant or Hertwig's anemia mouse model, congenital microcephaly as well as defects in the hematopoietic system, germ cells and eyes have been reported. The reduction in brain volume, particularly affecting gray matter, has been attributed mainly to disturbances in the proliferation and survival of early neuronal progenitors. In addition, defects in dendritic development and synaptogenesis exist that affect the excitation-inhibition balance. Here, we studied proteomic changes in cerebral cortices of <i>Cdk5rap2</i> mutant mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and methods</h3>\u0000 \u0000 <p>: We used large-gel two-dimensional gel (2-DE) electrophoresis to separate cortical proteins. 2-DE gels were visualized by a trained observer on a light box. Spot changes were considered with respect to presence/absence, quantitative variation and altered mobility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>: We identified a reduction in more than 30 proteins that play a role in processes such as cell cytoskeleton dynamics, cell cycle progression, ciliary functions and apoptosis. These proteome changes in the MCPH3 model can be associated with various functional and morphological alterations of the developing brain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>: Our results shed light on potential protein candidates for the disease-associated phenotype reported in MCPH3.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 1-2","pages":"50-62"},"PeriodicalIF":1.9,"publicationDate":"2022-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9129490","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":"High accuracy of single-molecule real-time sequencing in detecting a rare α-globin fusion gene in carrier screening population","authors":"Qiao-Miao Zhou,&nbsp;Fan Jiang,&nbsp;Jing Xu,&nbsp;Dan Lin,&nbsp;Ren-Liang Huang,&nbsp;Jian-Ying Zhou,&nbsp;Yan-Xia Qu,&nbsp;Dong-Zhi Li","doi":"10.1111/ahg.12486","DOIUrl":"10.1111/ahg.12486","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The α-globin fusion gene between the <i>HBA2</i> and <i>HBAP1</i> genes becomes clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combining with α⁰-thalassemia (α⁰-thal). Due to its uncommon rearrangement in the α gene cluster without dosage changes, this fusion gene is undetectable by common molecular testing approaches used for α-thal diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we used the single-molecule real-time (SMRT) sequencing technique to detect this fusion gene in 23 carriers identified by next-generation sequencing (NGS) among 16,504 screened individuals. Five primers for α and β thalassemia were utilized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>According to the NGS results, the 23 carriers include 14 pure heterozygotes, eight compound heterozygotes with common α-thal alleles, and one homozygote. By using SMRT, the fusion mutant was successfully detected in all 23 carriers. Furthermore, SMRT corrected the diagnosis in two “pure” heterozygotes: one was compound heterozygote with anti-3.7 triplication, and the other was homozygote.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results indicate that SMRT is a superior method compared to NGS in detecting the α fusion gene, attributing to its efficient, accurate, and one-step <i>properties</i>.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 1-2","pages":"9-17"},"PeriodicalIF":1.9,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9080963","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":"Segregation analysis identifies specific alpha-defensin (DEFA1A3) SNP–CNV haplotypes in predisposition to IgA nephropathy","authors":"Nzar A. A. Shwan,&nbsp;Eric C. Moise,&nbsp;Paula E. Necsoiu,&nbsp;Amy J. Farr,&nbsp;Daniel P. Gale,&nbsp;Jonathan Barratt,&nbsp;John A. L. Armour","doi":"10.1111/ahg.12481","DOIUrl":"10.1111/ahg.12481","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Immunoglobulin A (IgA) nephropathy is a disorder of the immune system affecting kidney function, and genome-wide association studies (GWAS) have defined numerous loci with associated variation, all implicating components of innate or adaptive immunity. Among these, single nucleotide polymorphisms (SNPs) in a region including the multiallelic copy number variation (CNV) of <i>DEFA1A3</i> are associated with IgA nephropathy in both European and Asian populations. At present, the precise factors underlying the observed associations at <i>DEFA1A3</i> have not been defined, although the key alleles differ between Asian and European populations, and multiple independent factors may be involved even within a single population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we measured <i>DEFA1A3</i> copy number in UK family trios with an offspring affected by IgA nephropathy, used the population distributions of joint SNP–CNV haplotypes to infer the likely segregation in trios, and applied transmission disequilibrium tests (TDT) to examine joint SNP–CNV haplotypes for over- or undertransmission into affected offspring from heterozygous parents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>We observed overtransmission of 3-copy class 2 haplotypes (raw <i>p</i> = 0.029) and some evidence for under-transmission of 3-copy class 1 haplotypes (raw <i>p</i> = 0.051), although these apparent effects were not statistically significant after correction for testing of multiple haplotypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 1-2","pages":"1-8"},"PeriodicalIF":1.9,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9422881","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":"Germline variants screening of MLH1, MSH2, MSH6 and PMS2 genes in 64 Algerian Lynch syndrome families: The first nationwide study","authors":"Asma-Lamia Boumehdi,&nbsp;Farid Cherbal,&nbsp;Feriel Khider,&nbsp;Mohammed Oukkal,&nbsp;Hassen Mahfouf,&nbsp;Ferhat Zebboudj,&nbsp;Mustapha Maaoui","doi":"10.1111/ahg.12482","DOIUrl":"10.1111/ahg.12482","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Colorectal cancer is the second leading cause of cancer-related deaths in women and men in Algeria. Lynch syndrome (LS) is an autosomal dominant disease caused by heterozygous germline pathogenic variants in mismatch repair genes (MMR) and frequently predisposes to colorectal cancer. However, data about MMR germline pathogenic variants in Algerian patients are limited. This first nationwide study aims to describe clinicopathologic features and germline variants in MMR genes in Algerian families with suspected LS. Sixty-four (64) families with suspected LS were studied. Index cases with LS who fulfilled Amsterdam criteria were screened by PCR-direct sequencing for germline variants in MMR genes: <i>MLH1</i> (exons 1, 9, 10, 13, 16), <i>MSH2</i> (exons 5, 6, 7, 12), <i>MSH6</i> (exons 4 and 8) and <i>PMS2</i> (exons 6 and 10). We selected these specific risk exons genes since they have a higher probability of harboring pathogenic variants. In addition, two unrelated LS patients were screened by next-generation sequencing using a cancer panel of 30 hereditary cancer genes. Six germline pathogenic variants and one germline likely pathogenic variant were identified in 19 (29.68%) families (4 <i>MLH1</i>, 2 <i>MSH2</i> and 1 <i>MSH6</i>). Of index cases and relatives who underwent genetic testing (<i>n</i> = 76), 30 (39.47%) had MMR pathogenic gene variants, one (0.13%) had MMR gene likely pathogenic variant and three had MMR variant of uncertain significance, respectively. Two novel germline pathogenic variants in <i>MLH1</i> (2) and one germline likely pathogenic variant in <i>MSH6</i> (1) never published in individuals with LS have been detected in the present study. The recurrent <i>MLH1</i> germline pathogenic variant c.1546C&gt;T has been found in nine LS families, six of them related with two large kindreds, from four North central provinces of Algeria. In addition, the common <i>MSH2</i> germline pathogenic variant c.942+3A&gt;T has been detected in five unrelated patients with a strong LS family history. The accumulative knowledge about clinicopathological and genetic characteristics of LS in Algerian patients will impact clinical management in the areas of both prevention and treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"328-352"},"PeriodicalIF":1.9,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33449476","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":"Study of variants in genes implicated in rare familial migraine syndromes and their association with migraine in 200,000 exome-sequenced UK Biobank participants","authors":"Katherine Alexis Markel,&nbsp;David Curtis","doi":"10.1111/ahg.12484","DOIUrl":"10.1111/ahg.12484","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A number of genes have been implicated in rare familial syndromes which have migraine as part of their phenotype but these genes have not previously been implicated in the common form of migraine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Among exome-sequenced participants in the UK Biobank, we identified 7194 migraine cases with the remaining 193,433 participants classified as controls. We investigated rare variants in 10 genes previously reported to be implicated in conditions with migraine as a prominent part of the phenotype and carried out gene- and variant-based tests for association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found no evidence for association of these genes or variants with the common form of migraine seen in our subjects. In particular, a frameshift variant in <i>KCNK18</i>, p.(Phe139Trpfs*24), which had been shown to segregate with migraine with aura in a multiply affected pedigree, was found in 196 (0.10%) controls as well as in 10 (0.14%) cases (<i>χ</i>² = 0.96, 1 df, <i>p</i> = 0.33).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Since there is no other reported evidence to implicate <i>KCNK18</i>, we conclude that this gene and its product, TRESK, should no longer be regarded as being involved in migraine aetiology. Overall, we do not find that rare, functional variants in genes previously implicated to be involved in familial syndromes including migraine as part of the phenotype make a contribution to the commoner forms of migraine observed in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"353-360"},"PeriodicalIF":1.9,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9915015","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":"A splice site variant in TCTN3 underlies an atypical form of orofaciodigital syndrome IV","authors":"Shabir Hussain,&nbsp;Shoaib Nawaz,&nbsp;Hammal Khan,&nbsp;Anushree Acharya,&nbsp;Isabelle Schrauwen,&nbsp;Wasim Ahmad,&nbsp;Suzanne M. Leal","doi":"10.1111/ahg.12462","DOIUrl":"10.1111/ahg.12462","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Orofaciodigital syndrome (OFD) is clinically heterogeneous and is characterized by abnormalities in the oral cavity, facial features, digits, and central nervous system. At least 18 subtypes of the condition have been described in the literature. OFD is caused by variants in several genes with overlapping phenotypes. We studied a consanguineous Pakistani family with two affected siblings with an atypical form of OFD type 4 (OFD4). In addition to the typical features of OFD4 that include limb defects and growth retardation, the siblings displayed rare features of scaphocephaly and seizures. Exome sequencing analysis revealed a novel homozygous splice site variant c.257-1G&gt;A in <i>TCTN3</i> that segregated with disease. This homozygous splice site variant in <i>TCTN3</i> is most likely the underlying cause of the atypical form of OFD4 observed in this family. Our results contribute to the phenotypic spectrum of <i>TCTN3</i> associated ciliopathies and will facilitate better clinical diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"291-296"},"PeriodicalIF":1.9,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/24/AHG-86-291.PMC9804382.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10823074","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":"A novel splicing variant in GALNS in mucopolysaccharidosis IVA and the necessity of re-evaluating primer sequences","authors":"Sang-Mi Kim,&nbsp;Eu Seon Noh,&nbsp;Jong-Ho Park,&nbsp;Hyung-Doo Park,&nbsp;Soo-Youn Lee,&nbsp;Ja-Hyun Jang,&nbsp;Sung Yoon Cho","doi":"10.1111/ahg.12483","DOIUrl":"10.1111/ahg.12483","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome type A) is an autosomal recessive disorder caused by defects in the lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (<i>GALNS</i>) gene, leading to progressive systemic skeletal dysplasia. Early diagnosis and early intervention with enzyme replacement therapy are crucial for improving outcomes in these patients. However, a relatively high number of patients are genetically undiagnosed due to high allelic heterogeneity and the absence of robust functional evidence for most variants of the <i>GALNS</i> gene. Herein, we report a novel intronic variant identified with RNA analysis and an allele dropout (ADO) event caused by a common benign variant in the primer-binding site in a Korean boy with MPS IVA.</p>\u0000 \u0000 <p>A 28-month-old boy presented with pectus carinatum, kyphoscoliosis, and joint hypermobility with multiple skeletal dysplasia involving the vertebrae and hip joint. Total urinary glycosaminoglycans were elevated with a predominant keratan sulfate fraction, and GALNS (EC 3.1.6.4) activity was significantly decreased in leukocytes. Sanger sequencing was performed; however, only one heterozygous intronic variant with uncertain clinical significance, c.566+3A &gt; T (p.(?)), was identified. As the patient exhibited clinical and biochemical features of MPS IVA, we conducted whole genome sequencing (WGS) of the patient and his family to clarify the molecular diagnosis. WGS revealed a compound heterozygous genotype, c.1019G &gt; A (p.(Gly340Asp)) and c.566+3A &gt; T (p.(?)), in the <i>GALNS</i> gene. On mRNA sequencing, c.566+3A &gt; T, was confirmed to cause exon 5 skipping and a premature stop codon. With subsequent investigation, we discovered that the variant, c.1019G &gt; A, was undetected on initial sequencing because of ADO due to a common benign variant (rs3859024:G &gt; C) at the primer annealing location.</p>\u0000 \u0000 <p>We present a novel intronic variant with a splicing defect in the <i>GALNS</i> gene and suggest that clinicians review primer sequences in cases not diagnosed on Sanger sequencing before progressing to diagnostic steps such as WGS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"361-368"},"PeriodicalIF":1.9,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40421604","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":"Applicability of the IrisPlex system for eye color prediction in an admixed population from Argentina","authors":"Diana María Hohl,&nbsp;Rebeca González,&nbsp;Gabriela Paula Di Santo Meztler,&nbsp;Jessica Patiño-Rico,&nbsp;Cristina Dejean,&nbsp;Sergio Avena,&nbsp;María De Los Ángeles Gutiérrez,&nbsp;Cecilia Inés Catanesi","doi":"10.1111/ahg.12480","DOIUrl":"10.1111/ahg.12480","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Eye color prediction based on an individual's genetic information is of interest in the field of forensic genetics. In recent years, researchers have studied different genes and markers associated with this externally visible characteristic and have developed methods for its prediction. The IrisPlex represents a validated tool for homogeneous populations, though its applicability in populations of mixed ancestry is limited, mainly regarding the prediction of intermediate eye colors. With the aim of validating the applicability of this system in an admixed population from Argentina (n = 302), we analyzed the six single nucleotide variants used in that multiplex for eye color and four additional SNPs, and evaluated its prediction ability. We also performed a genotype–phenotype association analysis. This system proved to be useful when dealing with the extreme ends of the eye color spectrum (blue and brown) but presented difficulties in determining the intermediate phenotypes (green), which were found in a large proportion of our population. We concluded that these genetic tools should be used with caution in admixed populations and that more studies are required in order to improve the prediction of intermediate phenotypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"297-327"},"PeriodicalIF":1.9,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40706536","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":"GR-α and GR-β mRNA levels in peripheral blood mononuclear cells of acute myelitis patients can assist in the identification of glucocorticoid sensitivity and are correlated with glucocorticoid therapeutic effect","authors":"Bolin Tang,&nbsp;Jun Han,&nbsp;Fen Wang,&nbsp;Xiang Li,&nbsp;Chaoyang Zhao","doi":"10.1111/ahg.12472","DOIUrl":"10.1111/ahg.12472","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Acute myelitis (AM) is a rare neuro-immune spinal cord disease. This study sought to explore the transcription level of glucocorticoid (GC) receptors α and β (GR-α/GR-β) in peripheral blood mononuclear cells (PBMCs) and their correlation with GC efficacy and sensitivity in AM patients. AM patients were grouped into the GC-sensitive group (<i>N</i> = 80) and GC-refractory group (<i>N</i> = 67). The GR-α and GR-β mRNA levels in PBMCs were detected. The differentiating value of GR-α, GR-β, and GR-α + GR-β on GC sensitivity and resistance in AM patients was assessed. The independent correlation between GR-α and GR-β mRNA levels and GC sensitivity in AM patients,t and the correlation between GR-α and GR-β mRNA levels and spinal function after GC treatment were analyzed. GR-α mRNA level in PBMCs of GC-refractory patients was lower than that of GC-sensitive patients, while GR-β mRNA level was higher than that of GC-sensitive patients. GR-α + GR-β mRNA had a high diagnostic value for GC sensitivity and resistance in AM patients (area under the ROC curve = 0.881, sensitivity = 79.1%, specificity = 85.0%). GR-α and GR-β mRNA levels were independently correlated with GC sensitivity. GR-α and GR-β mRNA levels were correlated with the spinal function of AM patients after GC treatment. Overall, GR-α and GR-β mRNA levels in PBMCs of AM patients can assist in the identification of GC sensitivity and are correlated with GC efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 5","pages":"268-277"},"PeriodicalIF":1.9,"publicationDate":"2022-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40178381","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}