Neurogenetics最新文献

{"title":"Clinical features of CNOT3-associated neurodevelopmental disorder in three Chinese patients.","authors":"Peiwei Zhao,&nbsp;Qingjie Meng,&nbsp;Chunhui Wan,&nbsp;Tao Lei,&nbsp;Lei Zhang,&nbsp;Xiankai Zhang,&nbsp;Li Tan,&nbsp;Hongmin Zhu,&nbsp;Xuelian He","doi":"10.1007/s10048-023-00713-z","DOIUrl":"https://doi.org/10.1007/s10048-023-00713-z","url":null,"abstract":"<p><p>CNOT3 is the central component of the CCR4-NOT protein complex, which is a global regulator of RNA polymerase II transcription. Loss of function mutations in CNOT3 lead to intellectual developmental disorder with speech delay, autism, and dysmorphic facies (IDDSADF), which is very rare. Herein, we reported two novel heterozygous frameshift mutations (c.1058_1059insT and c.724delT) and one novel splice site variant (c.387 + 2 T > C) in CNOT3 (NM_014516.3) gene in three Chinese patients with dysmorphic features, developmental delay, and behavior anomalies. The functional study showed that the CNOT3 mRNA levels were significantly decreased in the peripheral blood of two patients with c.1058_1059insT and c.387 + 2 T > C variants, respectively, and minigene assay demonstrated that the splice variant (c.387 + 2 T > C) resulted in exon skipping. We also found that CNOT3 deficiency was linked to alterations of expression levels of other CCR4-NOT complex subunits in mRNA level in the peripheral blood. By analyzing the clinical manifestations of all these patients with CNOT3 variants, including our three cases and 22 patients previously reported, we did not observe a correlation between genotypes and phenotypes. In summary, this is the first time to report cases with IDDSADF in the Chinese population, and three novel CNOT3 variants in these patients expand its mutational spectrum.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"129-136"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9292174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel KRIT1/CCM1 mutation accompanied by a NOTCH3 mutation in a Chinese family with multiple cerebral cavernous malformations.","authors":"Chunwang Li,&nbsp;Penghui Liu,&nbsp;Weilin Huang,&nbsp;Haojie Wang,&nbsp;Ke Ma,&nbsp;Lingyun Zhuo,&nbsp;Yaqing Kang,&nbsp;Qiu He,&nbsp;Yuanxiang Lin,&nbsp;Dezhi Kang,&nbsp;Fuxin Lin","doi":"10.1007/s10048-023-00714-y","DOIUrl":"https://doi.org/10.1007/s10048-023-00714-y","url":null,"abstract":"<p><p>Family cerebral cavernous malformations (FCCMs) are mainly inherited through the mutation of classical CCM genes, including CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. FCCMs can cause severe clinical symptoms, including epileptic seizures, intracranial hemorrhage (ICH), or functional neurological deficits (FNDs). In this study, we reported a novel mutation in KRIT1 accompanied by a NOTCH3 mutation in a Chinese family. This family consists of 8 members, 4 of whom had been diagnosed with CCMs using cerebral MRI (T1WI, T2WI, SWI). The proband (II-2) and her daughter (III-4) had intracerebral hemorrhage and refractory epilepsy, respectively. Based on whole-exome sequencing (WES) data and bioinformatics analysis from 4 patients with multiple CCMs and 2 normal first-degree relatives, a novel KRIT1 mutation, NG_012964.1 (NM_194456.1): c.1255-1G > T (splice-3), in intron 13 was considered a pathogenic gene in this family. Furthermore, based on 2 severe and 2 mild CCM patients, we found an SNV missense mutation, NG_009819.1 (NM_000435.2): c.1630C > T (p.R544C), in NOTCH3. Finally, the KRIT1 and NOTCH3 mutations were validated in 8 members using Sanger sequencing. This study revealed a novel KRIT1 mutation, NG_012964.1 (NM_194456.1): c.1255-1G > T (splice-3), in a Chinese CCM family, which had not been reported previously. Moreover, the NOTCH3 mutation NG_009819.1 (NM_000435.2): c.1630C > T (p.R544C) might be a second hit and associated with the progression of CCM lesions and severe clinical symptoms.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"137-146"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9292355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INPP4A-related genetic and phenotypic spectrum and functional relevance of subcellular targeting of INPP4A isoforms.","authors":"Laura Hecher,&nbsp;Frederike L Harms,&nbsp;Jasmin Lisfeld,&nbsp;Malik Alawi,&nbsp;Jonas Denecke,&nbsp;Kerstin Kutsche","doi":"10.1007/s10048-023-00709-9","DOIUrl":"https://doi.org/10.1007/s10048-023-00709-9","url":null,"abstract":"<p><p>Type I inositol polyphosphate-4-phosphatase (INPP4A) belongs to the group of phosphoinositide phosphatases controlling proliferation, apoptosis, and endosome function by hydrolyzing phosphatidylinositol 3,4-bisphosphate. INPP4A produces multiple transcripts encoding shorter and longer INPP4A isoforms with hydrophilic or hydrophobic C-terminus. Biallelic INPP4A truncating variants cause a spectrum of neurodevelopmental disorders ranging from moderate intellectual disability to postnatal microcephaly with developmental and epileptic encephalopathy and (ponto)cerebellar hypoplasia. We report a girl with the novel homozygous INPP4A variant NM_001134224.2:c.2840del/p.(Gly947Glufs*12) (isoform d). She presented with postnatal microcephaly, global developmental delay, visual impairment, myoclonic seizures, and pontocerebellar hypoplasia and died at the age of 27 months. The level of mutant INPP4A mRNAs in proband-derived leukocytes was comparable to controls suggesting production of C-terminally altered INPP4A isoforms. We transiently expressed eGFP-tagged INPP4A isoform a (NM_004027.3) wildtype and p.(Gly908Glufs*12) mutant [p.(Gly947Glufs*12) according to NM_001134224.2] as well as INPP4A isoform b (NM_001566.2) wildtype and p.(Asp915Alafs*2) mutant, previously reported in family members with moderate intellectual disability, in HeLa cells and determined their subcellular distributions. While INPP4A isoform a was preferentially found in perinuclear clusters co-localizing with the GTPase Rab5, isoform b showed a net-like distribution, possibly localizing near and/or on microtubules. Quantification of intracellular localization patterns of the two INPP4A mutants revealed significant differences compared with the respective wildtype and similarity with each other. Our data suggests an important non-redundant function of INPP4A isoforms with hydrophobic or hydrophilic C-terminus in the brain.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"79-93"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT.","authors":"Seyedeh Atiyeh Afjei,&nbsp;Mohammad Farid Mohammadi,&nbsp;Elham Pourbakhtyaran,&nbsp;Homa Ghabeli,&nbsp;Mahmoud Reza Ashrafi,&nbsp;Roya Haghighi,&nbsp;Maryam Rasulinezhad,&nbsp;Neda Pak,&nbsp;Ali Reza Tavasoli,&nbsp;Morteza Heidari","doi":"10.1007/s10048-022-00708-2","DOIUrl":"https://doi.org/10.1007/s10048-022-00708-2","url":null,"abstract":"<p><p>Guanidinoacetate methyltransferase deficiency (GAMTD) is a treatable neurodevelopmental disorder with normal or nonspecific imaging findings. Here, we reported a 14-month-old girl with GAMTD and novel findings on brain magnetic resonance imaging (MRI).A 14-‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍month-old female patient was referred to Myelin Disorders Clinic due to onset of seizures and developmental regression following routine vaccination at 4 months of age. Brain MRI, prior to initiation of treatment, showed high signal intensity in T2-weighted imaging in bilateral thalami, globus pallidus, subthalamic nuclei, substantia nigra, dentate nuclei, central tegmental tracts in the brainstem, and posterior periventricular white matter which was masquerading for mitochondrial leukodystrophy. Basic metabolic tests were normal except for low urine creatinine; however, exome sequencing identified a homozygous frameshift deletion variant [NM_000156: c.491del; (p.Gly164AlafsTer14)] in the GAMT. Biallelic pathogenic or likely pathogenic variants cause GAMTD. We confirmed the homozygous state for this variant in the proband, as well as the heterozygote state in the parents by Sanger sequencing.MRI features in GAMTD can mimic mitochondrial leukodystrophy. Pediatric neurologists should be aware of variable MRI findings in GAMTD since they would be misleading to other diagnoses.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"67-78"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurogenetics: Current Topics in Cellular and Developmental Neurobiology","authors":"","doi":"10.1007/978-3-031-07793-7","DOIUrl":"https://doi.org/10.1007/978-3-031-07793-7","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"51 2","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50986405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating the phenotype and genetic basis of AMPD2-related pontocerebellar hypoplasia.","authors":"Tal Gilboa,&nbsp;Naama Elefant,&nbsp;Vardiella Meiner,&nbsp;Nuphar Hacohen","doi":"10.1007/s10048-022-00706-4","DOIUrl":"https://doi.org/10.1007/s10048-022-00706-4","url":null,"abstract":"<p><p>Pontocerebellar hypoplasia is a group of disorders with a wide range of presentations. We describe here the genetic and phenotypic features of PCH type 9 due to mutations in AMPD2. All patients have severe intellectual disability, and the vast majority manifest abnormal tone, cortical blindness, and microcephaly. Almost all have agenesis of the corpus callosum and severe cerebellar hypoplasia. The course is not progressive, however, few die in the first decade of life. Mutations are spread throughout the gene, and no hot spot can be identified. One of the mutations we report here is the most distal truncating variant known in this gene and is predicted to result in a truncated protein. The phenotype is severe in all cases; thus, no clear genotype-phenotype correlation can be established.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 1","pages":"61-66"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10775834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole exome screening of neurodevelopmental regression disorders in a cohort of Egyptian patients.","authors":"Miral M Refeat,&nbsp;Walaa El Naggar,&nbsp;Mostafa M El Saied,&nbsp;Ayman Kilany","doi":"10.1007/s10048-022-00703-7","DOIUrl":"https://doi.org/10.1007/s10048-022-00703-7","url":null,"abstract":"<p><p>Developmental regression describes a child who begins to lose his previously acquired milestones skills after he has reached a certain developmental stage and though affects his childhood development. It is associated with neurodegenerative diseases including leukodystrophy and neuronal ceroid lipofuscinosis diseases (NCLs), one of the most frequent childhood-onset neurodegenerative disorders. The current study focused on screening causative genes of developmental regression diseases comprising neurodegenerative disorders in Egyptian patients using next-generation sequencing (NGS)-based analyses as well as developing checklist to support clinicians who are not familiar with these diseases. A total of 763 Egyptian children (1 to 11 years), mainly diagnosed with developmental regression, seizures, or visual impairment, were studied using whole exome sequencing (WES). Among 763 Egyptian children, 726 cases were early clinically and molecularly diagnosed, including 482 cases that had pediatric stroke, congenital infection, and hepatic encephalopathy; meanwhile, 192 had clearly dysmorphic features, 31 showed central nervous system (CNS) malformation, 17 were diagnosed by leukodystrophy, 2 had ataxia telangiectasia, and 2 were diagnosed with tuberous sclerosis. The remained 37 out of 763 candidates were suspected with NCLs symptoms; however, 28 were confirmed to be NCLs patients, 1 was Kaya-Barakat-Masson syndrome, 1 was diagnosed as infantile neuroaxonal dystrophy, and 7 cases required further molecular diagnosis. This study provided an NGS-based approach of the genetic causes of developmental regression and neurodegenerative diseases as it comprised different variants and de novo mutations with complex phenotypes of these diseases which in turn help in early diagnoses and counseling for affected families.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 1","pages":"17-28"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9823068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of different spectra of NOTCH3 variants on the clinical phenotype of CADASIL - experience from Slovakia.","authors":"M Juhosová,&nbsp;J Chandoga,&nbsp;F Cisárik,&nbsp;S Dallemule,&nbsp;P Ďurina,&nbsp;D Jarásková,&nbsp;P Jungová,&nbsp;D Kantarská,&nbsp;M Kvasnicová,&nbsp;M Mistrík,&nbsp;A Pastoráková,&nbsp;R Petrovič,&nbsp;A Valachová,&nbsp;H Zelinková,&nbsp;J Barošová,&nbsp;D Böhmer,&nbsp;J Štofko","doi":"10.1007/s10048-022-00704-6","DOIUrl":"https://doi.org/10.1007/s10048-022-00704-6","url":null,"abstract":"<p><p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular disorder causing ischaemic attacks and strokes in middle-aged adults. Though the clinical spectrum includes some typical symptoms, recognition of the disease, especially at an earlier stage, is very difficult because of the highly variable manifestation and incomplete clinical picture. Characteristic brain MRI findings and the presence of pathogenic variants in the NOTCH3 gene are fundamental for CADASIL diagnosis. In this paper, we provide the first comprehensive report on CADASIL patients from Slovakia. Altogether, we identified 23 different pathogenic variants in 35 unrelated families. In our cohort of patients with clinical suspicion of CADASIL, we found a causal genetic defect and confirmed the diagnosis in 10.2% of cases. We present the case reports with up-to-date unpublished NOTCH3 variants and describe their phenotype-genotype correlation: p.(Cys65Phe), p.(Pro86Leu/Ser502Phe), p.(Arg156*), p.(Cys408Arg), p.(Tyr423Cys), p.(Asp1720His), and p.(Asp1893Thrfs*13). The most frequently described location for pathogenic variants was in exon 4, whereas the most common single variant was p.Arg1076Cys in exon 20. Based on the results of our study, we propose a re-evaluation of the criteria for the selection of patients suitable for NOTCH3 gene analysis. We hereby state that the currently used protocol of a high score requirement is not ideal for assessing molecular analysis, and it will be desirable to be less strict in criteria for genetic testing.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 1","pages":"1-16"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10777086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-phenotype correlation and natural history study of dysferlinopathy: a single-centre experience from India.","authors":"Saraswati Nashi,&nbsp;Kiran Polavarapu,&nbsp;Mainak Bardhan,&nbsp;Ram Murthy Anjanappa,&nbsp;Veeramani Preethish-Kumar,&nbsp;Seena Vengalil,&nbsp;Hansashree Padmanabha,&nbsp;Thenral S Geetha,&nbsp;P V Prathyusha,&nbsp;Vedam Ramprasad,&nbsp;Aditi Joshi,&nbsp;Tanushree Chawla,&nbsp;Gopikirshnan Unnikrishnan,&nbsp;Pooja Sharma,&nbsp;Akshata Huddar,&nbsp;Bharathram Uppilli,&nbsp;Abel Thomas,&nbsp;Dipti Baskar,&nbsp;Susi Mathew,&nbsp;Deepak Menon,&nbsp;Gautham Arunachal,&nbsp;Mohammed Faruq,&nbsp;Kumarasamy Thangaraj,&nbsp;Atchayaram Nalini","doi":"10.1007/s10048-022-00707-3","DOIUrl":"https://doi.org/10.1007/s10048-022-00707-3","url":null,"abstract":"<p><p>Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies. We analysed a retrospective cohort of patients with dysferlinopathy from a single quaternary care centre in India. A total of 124 patients with dysferlinopathy were included (40 females). Median age at onset and duration of illness were 21 years (range, 13-50) and 48 months (range, 8-288), respectively. The average follow-up period was 60 months (range, 12-288). Fifty-one percent had LGMD pattern of weakness at onset; 23.4% each had Miyoshi and proximo-distal type while isolated hyperCKemia was noted in 1.6%. About 60% were born to consanguineous parents and 26.6% had family history of similar illness. Twenty-three patients (18.6%) lost ambulation at follow-up; the median time to loss of independent ambulation was 120 months (range, 72-264). Single-nucleotide variants (SNVs) constituted 78.2% of patients; INDELs 14.5% and 7.3% had both SNVs and INDELs. Earlier age at onset was noted with SNVs. There was no correlation between the other clinical parameters and ambulatory status with the genotype. Thirty-seven (45.7%) novel pathogenic/likely pathogenic (P/LP) variants were identified out of a total of 81 variations. The c.3191G > A variant was the most recurrent mutation. Our cohort constitutes a clinically and genetically heterogeneous group of dysferlinopathies. There is no significant correlation between the clinico-genetic profile and the ambulatory status.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 1","pages":"43-53"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9339911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural variation and eQTL analysis in two experimental populations of chickens divergently selected for feather-pecking behavior.","authors":"Clemens Falker-Gieske,&nbsp;Jörn Bennewitz,&nbsp;Jens Tetens","doi":"10.1007/s10048-022-00705-5","DOIUrl":"https://doi.org/10.1007/s10048-022-00705-5","url":null,"abstract":"<p><p>Feather pecking (FP) is a damaging nonaggressive behavior in laying hens with a heritable component. Its occurrence has been linked to the immune system, the circadian clock, and foraging behavior. Furthermore, dysregulation of miRNA biogenesis, disturbance of the gamma-aminobutyric acid (GABAergic) system, as well as neurodevelopmental deficiencies are currently under debate as factors influencing the propensity for FP behavior. Past studies, which focused on the dissection of the genetic factors involved in FP, relied on single nucleotide polymorphisms (SNPs) and short insertions and deletions < 50 bp (InDels). These variant classes only represent a certain fraction of the genetic variation of an organism. Hence, we reanalyzed whole-genome sequencing data from two experimental populations, which have been divergently selected for FP behavior for over more than 15 generations, performed variant calling for structural variants (SVs) as well as tandem repeats (TRs), and jointly analyzed the data with SNPs and InDels. Genotype imputation and subsequent genome-wide association studies, in combination with expression quantitative trait loci analysis, led to the discovery of multiple variants influencing the GABAergic system. These include a significantly associated TR downstream of the GABA receptor subunit beta-3 (GABRB3) gene, two microRNAs targeting several GABA receptor genes, and dystrophin (DMD), a direct regulator of GABA receptor clustering. Furthermore, we found the transcription factor ETV1 to be associated with the differential expression of 23 genes, which points toward a role of ETV1, together with SMAD4 and KLF14, in the disturbed neurodevelopment of high-feather pecking chickens.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 1","pages":"29-41"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9823035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10772658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}