Genetic Analysis Research Articles

Identification of a cryptic unbalanced translocation Der(22)t(12;22)(q24.33;q13.33) in a large Chinese family with Phelan-McDermid syndrome by nanopore sequencing

To explore the genetic cause of a four-generation severe intellectual disability in a Chinese family using nanopore sequencing and to provide genetic counseling and reproductive guidance for family members. Multiple genetic analyses of the proband and family members were performed, including chromosome karyotype analysis, whole exome sequencing, nanopore sequencing, PCR amplification, and Sanger sequencing. The results of G-binding karyotyping, CGG repeats for FMR1, GGC repeats for NOTCH2NCL, and trio-whole-exome sequencing were negative for the proband and his parents. Nanopore sequencing showed that the proband carried 12q24.33 microduplication (3.26 Mb) and 22q13.33 microdeletion (1.5 Mb). According to the guidelines of the American Society for Medical Genetics and Genomics (ACMG), the 22q13.33 microdeletion was classified as pathogenic, whereas the 12q24.33 microduplication was classified as a variant of uncertain significance (VUS). The precise karyotype and location of chromosomal breakpoints in the patient and family members were determined through PCR. According to the results of Sanger sequencing, a cryptic balanced translocation was detected in the proband’s father. Additionally, informative SNPs were identified near the breakpoints for preimplantation genetic testing for structure rearrangement (PGT-SR) treatment by nanopore sequencing. We identified a cryptic unbalanced translocation in a large Chinese family with Phelan-McDermid syndrome (22q13.33 deletion syndrome) by nanopore sequencing. Nanopore sequencing can be a powerful tool for the genetic diagnosis of unexplained intellectual disability and the detection of precise breakpoints of chromosomal rearrangement in PGT-SR treatment.

Sleep quality among sample of Egyptian patients with Alzheimer’s disease: risk factors and role of genetic profiling for ACE, ACE 2 and APO E genotypes

BackgroundMost individuals having Alzheimer’s disease generally experience increased frequency of awakenings as well as prolonged wakefulness periods at night. Brain wave research indicate reductions in both REM (dreaming stage) along with NREM (non-dreaming stage). The inherited pattern of Alzheimer’s disease is attributed to presence of genetic polymorphisms. The association of these polymorphisms and sleep pattern in Alzheimer’s disease patients was not assessed before.PurposeThis research was aimed at assessing the association between sleep quality as well as genetic polymorphisms of ACE, ACE2 and Apo E among Alzheimer’s disease patients in Upper Egypt.Patients and methodsOur cross-sectional study with analytic component involved 50 cases having Alzheimer’s disease evaluated utilizing Pittsburg sleep quality index for sleep quality. They were accordingly divided into good as well as poor sleep quality groups. Genetic analysis of ACE, ACE2 (rs2285666) SNPs and Apo E (rs121918398) SNPs was done using (RFLP-PCR) I.ResultsNo statistically significant variation was documented among both groups regarding age as well as age at diagnosis. Female patients were more susceptible for poor sleep quality. In addition, patients came from rural areas were significantly higher among poor sleep quality group. Statistical significant variations were documented among both groups as regard presenting symptoms and HAM-A and HAM-D. No statistically significant variations were documented among both groups as regard ACE genotypes; however, ACE 2 AA genotype and A allele were higher with statistically significant difference among poor sleep quality group. Apo E3/E4 genotype and E4 allele were greater with statistically significant variations among poor sleep quality group.ConclusionsFemale patient and rural Alzheimer’s disease patients at high risk for poor sleep quality. In addition, Apo E4 carriers and ACE2 AA carriers are at increasing susceptibility for poor sleep quality.

Parasite fauna of Lake Biwa water system: A review on parasites using aquatic host organisms in their life cycle.

Lake Biwa, with its long geological history, has given rise to many endemic species, but only four endemic parasites are known from Lake Biwa and connected water areas. They are considered to have co-evolved with their endemic host species or to have become adapted to the pelagic ecosystem unique to Lake Biwa. The number of parasite species introduced into this water system is rising, facilitated not only by the introduction of new species but also through genetic analyses that have revealed new information about previously known species. In addition, a few species are considered to have become extinct in the lake recently. Parasitological surveys of under-studied host taxa and more genetic studies are essential not only to understand the fauna of the Lake Biwa water system, but also to investigate parasite life cycles and host-parasite coevolution.

Demographic and historical processes influencing Cochliomyia hominivorax (Diptera: Calliphoridae) population structure across South America

BackgroundIn this study, we investigated the genetic variability and population structure of the New World screwworm fly Cochliomyia hominivorax. We tested the hypothesis that the species exhibits a center–periphery distribution of genetic variability, with higher genetic diversity in central populations (e.g., Brazil) and lower diversity in peripheral populations.MethodsUsing microsatellite markers, we analyzed larvae collected from infested livestock across South America. The larvae were collected directly from various wound sites to ensure a broad representation of genetic diversity.ResultsContrary to our initial hypothesis, the results revealed consistent genetic variability across the species’ distribution, low population differentiation, and no evidence of isolation-by-distance patterns among subpopulations. The genetic analysis indicated an excess of homozygotes, potentially due to the Wahlund effect, null alleles, or selection pressure.ConclusionsThese findings suggest a complex metapopulation structure for C. hominivorax, challenging classical population genetics models. This complexity likely arises from the species’ high dispersal capability and frequent local extinctions followed by recolonization. These results have important implications for the design and implementation of control programs, emphasizing the need for coordinated and large-scale actions rather than isolated initiatives.Graphical

Assessing genetic diversity and population structure of f4:f5 wheat genotypes using morphological and microsatellite markers under heat stress

Diversity in the plant gene pool provides breeders with the opportunity to improve targeted traits. Enhancing the genetic background through the introgression of desired gene(s) is an effective strategy to combat stresses like heat. Two field experiments were carried out in 2019–20 and 2020–21 at the research fields of Genetics and Plant Breeding at Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh, to identify heat-tolerant wheat advance lines. In F4 generation, 60 advanced lines were selected from a pool of 160 line and in the F5 generation, 16 lines were selected from the previous selection. Analysis of variance revealed significant variation in both the F4 and F5 generations, with the F5 populations outperforming the check varieties. Grain weight demonstrated the highest heritability and genetic advance, while the plant yield exhibited moderate to high performance. Plant height had the most significant direct effect at the genotypic level, while grain weight had the highest impact at the phenotypic level. A total of 77 alleles were identified with an average of 4.53 alleles per locus. The genetic similarity analysis showed that Shatabdi and BARI Gom 25 had the highest similarity at 94%, followed by P3-18-10 with P3-11-3 at 90%, and P3-24-10 with P3-21-10 at 85%. The PCA, structural, and dendrogram analyses all indicated the same grouping of the selected lines. Therefore, selecting of these lines for the F6 generation would enhance resilience against heat stress.

Mapping the cellular etiology of schizophrenia and complex brain phenotypes.

Psychiatric disorders are multifactorial and effective treatments are lacking. Probable contributing factors to the challenges in therapeutic development include the complexity of the human brain and the high polygenicity of psychiatric disorders. Combining well-powered genome-wide and brain-wide genetics and transcriptomics analyses can deepen our understanding of the etiology of psychiatric disorders. Here, we leverage two landmark resources to infer the cell types involved in the etiology of schizophrenia, other psychiatric disorders and informative comparison of brain phenotypes. We found both cortical and subcortical neuronal associations for schizophrenia, bipolar disorder and depression. These cell types included somatostatin interneurons, excitatory neurons from the retrosplenial cortex and eccentric medium spiny-like neurons from the amygdala. In contrast we found T cell and B cell associations with multiple sclerosis and microglial associations with Alzheimer's disease. We provide a framework for a cell-type-based classification system that can lead to drug repurposing or development opportunities and personalized treatments. This work formalizes a data-driven, cellular and molecular model of complex brain disorders.

Studies on Marker-Trait Association for High Flavonoid Content in Rice through Genetic, Molecular and Biochemical Analysis

Studies on Marker-Trait Association for High Flavonoid Content in Rice through Genetic, Molecular and Biochemical Analysis

Clinical and genetic analysis of a Chinese family with GM1 gangliosidosis caused by a novel mutation in GLB1 gene

Clinical and genetic analysis of a Chinese family with GM1 gangliosidosis caused by a novel mutation in GLB1 gene

The allelic mutation of NBS-LRR gene causes premature senescence in wheat.

Premature senescence has a significant impact on the yield and quality of wheat crops. The process is controlled by multiple and intricate genetic pathways and regulatory elements, whereby the discovery of additional mutants provides important insights into the molecular basis of this important trait. Here, we developed a premature senescence wheat mutant je0874, its leaves started to show yellow before heading stage; with plant growth and development, the degree of yellowing worsened rapidly, and chlorophyll content in flag leaf was reduced by 93.8% at 15 days after heading, all other leaves became dryness at the grain filling stage. In the mutant, the reactive oxygen species (ROS) and its metabolites increased up to 34.8%~47.3%, while activities of ROS scavenging enzymes were reduced by 62.7% to 96.7%. Premature senescence resulted in a reduction of thousand grain weight by over 50%. Genetic analysis showed the mutation of senescence was controlled by a single recessive gene, and target gene was finely mapped to a 338kb region of the long arm of chromosome 2D. This region contained a total of 6 annotated genes, while only gene TraesFLD2D01G513900 carried a SNP mutation. The gene contained an NBS-LRR domain, we named it Taps1. Allelic mutants of Taps1 exhibited a lesion mimic phenotype, and the mutant allele resulted in cell death in tobacco, which represent a novel gene controlling wheat senescence. Two haplotypes were identified in 180 accessions, which did not lead to cell death. These results contribute to increase our understanding of the regulation of premature plant senescence.

Whole Exome Sequencing Reveals Candidate Variants in Ion Channel Genes for Pelvic Muscle Dysfunction in Young Females with a Family History.

Pelvic floor dysfunction usually results in pelvic organ prolapse (POP) and/or urinary incontinence. In women, several factors, including pregnancy and vaginal delivery, can affect pelvic muscle conditions. The aim of the study was to perform a genetic analysis in young women with a family history of pelvic floor dysfunction to find potentially harmful variants or variants that increase the risk of developing pelvic floor disorders. We employed whole exome sequencing to test ten young women with pelvic floor muscle dysfunction (along with their parents) and a family history. The average age of symptoms was 29.1 (± 3.98) years old, soon after their first delivery. In five out of ten patients, trio-based WES analysis revealed potentially pathogenic, causative nonsense variants in ion channel genes, including ATP1A4, CLCN1, GRIN2C, and ORAI1, as well as missense variants in PIEZO1 and RYR1. Additionally, some of these patients had variants in genes related to muscle function (MUSK) and connective tissue disorder (FKBP14, p.Glu122ArgfsTer7). The variants found in this study, such as CLCN1 (p.Arg894Ter) and MUSK (p.Val790Met), have already been associated with neuromuscular channelopathy and severe muscle weakness. The identified candidate genes encode mainly proteins involved in electrical action potential and mechanical muscle contraction. The results suggest that the identified genetic variants may result in skeletal muscle ion channelopathies that affect muscle function, gradually leading to muscle hypotonia and weakness.

Population genetic analysis of clinical Mycobacterium abscessus complex strains in China

Population genetic analysis of clinical Mycobacterium abscessus complex strains in China

Increased risk of hypertrophic scarring in estrogen receptor-positive breast cancer: a bidirectional mendelian randomization study.

Breast cancer (BC) is a prevalent malignancy in women, often necessitating tumor resection and breast reconstruction surgeries. However, the post-operation scars can be of concern, as hypertrophic scars (HS) can profoundly impact patients' quality of life. Our study used the bidirectional Mendelian randomization (MR) method to explore the potential relationship between BC and HS. We conducted a comprehensive genetic analysis using a large meta-analysis dataset comprising the BCAC, FinnGen, MRC-IEU, and GTEx eQTL datasets. We identified independent genetic loci associated with BC and HS among individuals of European ancestry. These loci served as instrumental variables (SNPs) in MR analysis. We used the inverse-variance weighted and weighted median methods, with the odds ratio (OR) as the effect measure, to investigate the causal relationship between breast disease and HS, and all significance was corrected by FDR and Bonferroni. We assessed heterogeneity and horizontal pleiotropy through Cochran's Q, MR-PRESSO, and MR-Egger intercept tests. Moreover, a leave-one-out sensitivity analysis was performed to evaluate the impact of individual SNPs on the MR study. The MR analysis showed a significant positive association between BC and HS (OR = 1.31, 95% CI 1.10-1.56, P = 0.002). However, there was no significant association between benign breast neoplasm and HS (OR = 0.97, P = 0.73). Subgroup analysis of BC revealed that estrogen receptor-positive (ER+) BC increased the risk of HS (OR = 1.32, 95% confidence interval: 1.11-1.57, P = 0.0016), while ER-negative (ER-) BC did not increase the risk of HS (OR = 0.99, P = 0.91). Analysis of the GTEx database demonstrated that increased ER level alone in healthy individuals (n = 3301) did not increase the risk of HS (P = 0.42). This result was well replicated in two independent HS datasets, and the causal effect of BC on HS was unidirectional. BC is positively associated with the incidence of HS, especially in the case of ER+BC. However, there is a lack of substantial evidence regarding the relationship between ER-BC and HS.

Circadian rhythm and lithium response in bipolar disorder: Insights from actigraphy and NR1D1 polymorphism

ABSTRACT Lithium has long been used as a cornerstone mood stabilizer in the treatment of bipolar disorder (BD). However, reliable biomarkers that can predict which patients will respond better to lithium are still lacking. This study aims to evaluate the potential of NR1D1 gene SNP; rs2071427 and actigraphic measurements in predicting lithium response. Thirty-one patients diagnosed with BD at Selçuk University Faculty of Medicine and who were euthymic for at least 8 weeks were included in the study. Sleep-wake cycles and circadian rhythms of the participants were monitored by actigraph for approximately 1 week. For genetic analyses, the SNP rs2071427 variant of the NR1D1 gene was evaluated. A significant proportion of patients with homozygous (AA/GG) genotypes responded well to lithium, whereas some patients with heterozygous (AG) genotypes did not respond to lithium. Actigraphic data showed that there were marked variations in the sleep patterns of BD patients. The Morningness-Eveningness Questionnaire scale did not adequately discriminate the morning chronotype. Seasonal Pattern Assessment Questionnaire results showed that most patients had a seasonal pattern, but this was insufficient to predict response to lithium. This study once again demonstrates the need for new biomarkers to predict lithium response. The findings are an important step in the personalization of BD treatment and may improve treatment efficacy and minimize side effects by tailoring the treatment process to the individual characteristics of patients. Future studies should support these findings with larger sample groups and studies on different genetic markers.

ABCA6 Regulates Chondrogenesis and Inhibits Joint Degeneration via Orchestrated Cholesterol Efflux and Cellular Senescence.

Patellar dysplasia (PD) can cause patellar dislocation and subsequent osteoarthritis (OA) development. Herein, a novel ABCA6 mutation contributing to a four-generation family with familiar patellar dysplasia (FPD) is identified. In this study, whole exome sequencing (WES) and genetic linkage analysis across a four-generation lineage presenting with six cases of FPD are conducted. A disease-causing mutation in ABCA6 is identified for FPD. Further analyses reveal a consistent correlation between ABCA6 expression downregulation and PD occurrence, chondrocyte degeneration, and OA onset. Moreover, ABCA6-KO mice demonstrate severe knee joint degeneration and accelerated OA progression. Besides, synovial mesenchymal stem cells (SMSCs) are extracted from WT, ABCA6-/+, and ABCA6-/- mice to create chondrogenic organoids in vitro, confirming ABCA6 deficiency can lead to chondrocyte degeneration via modulating cell cycle and activating cellular senescence. Moreover, transcriptome and metabolomic sequencing analysis on ABCA6-KO chondrocytes unveils that the ABCA6 deficiency inhibits cholesterol efflux, leading to intracellular cholesterol accumulation and subsequent cellular senescence and impaired chondrogenesis.A disease-causing mutation of ABCA6 is identified for FPD. ABCA6 is correlated with PD occurrence and subsequent OA progression. ABCA6 can serve as a potential target in chondrogenesis and OA treatment by orchestrated intracellular cholesterol efflux and delayed cellular senescence.

Integrative genetics and multiomics analysis reveal mechanisms and therapeutic targets in vitiligo highlighting JAK STAT pathway regulation of CTSS

Vitiligo is a complex autoimmune disease characterized by the loss of melanocytes, leading to skin depigmentation. Despite advances in understanding its genetic and molecular basis, the precise mechanisms driving vitiligo remain elusive. Integrating multiple layers of omics data can provide a comprehensive view of disease pathogenesis and identify potential therapeutic targets. The study aims to delineate the genetic and molecular mechanisms of vitiligo pathogenesis using an integrative multiomics strategy. We focus on exploring the regulatory influence of the JAK/STAT pathway on Cathepsin S, a potential therapeutic target in vitiligo. Our GWAS-meta analysis pinpointed five druggable genes: ERBB3, RHOH, CDK10, MC1R, and NDUFAF3, and underwent drug target exploration and molecular docking. SMR analysis linked CTSS, CTSH, STX8, KIR2DL3, and GRHPR to vitiligo through pQTL and eQTL associations. Microarray and single-cell RNA-seq data showed differential expression of CTSS and STAT1/3 in vitiligo patients’ blood and skin lesions. Our study offers novel perspectives on vitiligo’s genetic and molecular basis, highlighting the JAK/STAT pathway’s role in regulating CTSS for antigen processing in melanocytes. Further research is needed to confirm these results and assess the therapeutic potential of CTSS and related genes.

Common Ancestry of the Id Locus: Chromosomal Rearrangement and Polygenic Possibilities.

The diversity in dermal pigmentation and plumage color among domestic chickens is striking, with Black Bone Chickens (BBC) particularly notable for their intense melanin hyperpigmentation. This unique trait is driven by a complex chromosomal rearrangement on chromosome 20 at the Fm locus, resulting in the overexpression of the EDN3 (a gene central to melanocyte regulation). In contrast, the inhibition of dermal pigmentation is regulated by theId locus. Although prior studies using genetic crosses, GWAS, and gene expression analysis have investigated the genetic underpinnings of the Id locus, its precise location and functional details remain elusive. Our study aims to precisely locate the Id locus, identify associated chromosomal rearrangements and candidate genes influencing dermal pigmentation, and examine the ancestral status of the Id locus in BBC breeds. Using public genomic data from BBC and non-BBC breeds, we refined the Id locus to a ~1.6Mb region that co-localizes with Z amplicon repeat units at the distal end of the q-arm of chromosome Z within a 10.36Mb inversion in Silkie BBC. Phylogenetic and population structure analyses reveal that the Id locus shares a common ancestry across all BBC breeds, much like the Fm locus. Selection signatures and highly differentiated BBC-specific SNPs within the MTAP gene position it as the prime candidate for the Id locus with CCDC112 and additional genes, suggesting a possible polygenic nature. Our results suggest that the Id locus is shared among BBC breeds and may function as asupergene cluster in shank and dermal pigmentation variation.

Multiple, Single Trait GWAS and Supervised Machine Learning Reveal the Genetic Architecture of Fraxinus excelsior Tolerance to Ash Dieback in Europe.

Common ash (Fraxinus excelsior) is under intensive attack from the invasive alien pathogenic fungus Hymenoscyphus fraxineus, causing ash dieback at epidemic levels throughout Europe. Previous studies have found significant genetic variation among genotypes in ash dieback susceptibility and that host phenology, such as autumn yellowing, is correlated with susceptibility of ash trees to H. fraxineus; however, the genomic basis of ash dieback tolerance in F. excelsior requires further investigation. Here, we integrate quantitative genetics based on multiple replicates and genome-wide association analyses with machine learning to reveal the genetic architecture of ash dieback tolerance and of phenological traits in F. excelsior populations in six European countries (Austria, Denmark, Germany, Ireland, Lithuania, Sweden). Based on phenotypic data of 486 F. excelsior replicated genotypes we observed negative genotypic correlations between crown damage caused by ash dieback and intensity of autumn leaf yellowing within multiple sampling sites. Our results suggest that the examined traits are polygenic and using genomic prediction models, with ranked single nucleotide polymorphisms (SNPs) based on GWAS associations as input, a large proportion of the variation was predicted by unlinked SNPs. Based on 100 unlinked SNPs, we can predict 55% of the variation in disease tolerance among genotypes (as phenotyped in genetic trials), increasing to a maximum of 63% when predicted from 9155 SNPs. In autumn leaf yellowing, 52% of variation is predicted by 100 unlinked SNPs, reaching a peak of 72% using 3740 SNPs. Based on feature permutations within genomic prediction models, a total of eight nonsynonymous SNPs linked to ash dieback crown damage and autumn leaf yellowing (three and five SNPs, respectively) were identified, these were located within genes related to plant defence (pattern triggered immunity, pathogen detection) and phenology (regulation of flowering and seed maturation, auxin transport). We did not find an overlap between genes associated with crown damage level and autumn leaf yellowing. Hence, our results shed light on the difference in the genomic basis of ADB tolerance and autumn leaf yellowing despite these two traits being correlated in quantitative genetic analysis. Overall, our methods show the applicability of genomic prediction models when combined with GWAS to reveal the genomic architecture of polygenic disease tolerance enabling the identification of ash dieback tolerant trees for breeding or conservation purposes.

Prenatal phenotype of PNKP-related microcephaly, seizures, and developmental delay: A case report and literature review.

Microcephaly, epilepsy, and developmental delay (MCSZ) is a rare neurodevelopmental disorder associated with autosomal recessive inheritance of mutations in the polynucleotide kinase 3'-phosphatase (PNKP) gene. Prompt identification and management are essential, as delayed diagnosis or intervention may result in severe complications or mortality. In this case, prenatal screening in the second trimester detected fetal microcephaly with a gradual decline in head circumference, prompting the decision to terminate the pregnancy. Subsequent genetic analysis of the fetal tissue confirmed the presence of compound heterozygous mutations in the PNKP gene. The patient, a 34-year-old remarried female with no history of consanguineous marriage, underwent 2 mid-trimester termination procedures due to fetal microcephaly and sought counseling for reproductive assistance. The patient's carrier status for PNKP mutations was ascertained through whole-exome sequencing of the termination tissue and molecular genetic testing for monogenic disorders. The terminated fetus was diagnosed with MCSZ, a condition associated with compound heterozygous mutations in the PNKP gene. Fetal microcephaly was identified via mid-trimester prenatal ultrasound, leading to the termination of the pregnancy during the same trimester. Subsequent genetic analysis of the immediate family revealed compound heterozygous mutations in the PNKP gene as the underlying cause of MCSZ. Genetic counseling was provided, followed by 1 cycle of preimplantation genetic testing for monogenic. The patient carried the heterozygous c.1188 + 1G > A PNKP mutation, whereas her husband carried the heterozygous c.976G > A PNKP mutation. The fetus was found to have compound heterozygous mutations c.976G > A and c.1188 + 1G > A. After counseling, the couple underwent 1 cycle of preimplantation genetic testing for monogenic, unfortunately, no pregnancy occurred after the 2 embryos were transferred. MCSZ, a condition caused by PNKP mutations, is exceedingly rare. Women with a history of adverse pregnancy outcomes should undergo close monitoring during prenatal checkups. If fetal microcephaly is detected, it is essential to strictly follow obstetric guidelines for prenatal care, such as comprehensive cranial magnetic resonance imaging and genetic testing for confirmation. Avoidance of consanguineous marriages is advised. Early detection and timely intervention are key to preventing adverse pregnancy outcomes.

Evaluation of the Frequency of HLA-DQ2/DQ8 Genes Among Patients with Celiac Disease and Those on a Gluten-Free Diet.

Celiac disease (CD) is a chronic, permanent, gluten-dependent disease that manifests itself with inflammation of the small intestine and malabsorption in genetically predisposed individuals with HLA-DQ2 and -DQ8 (human leukocyte antigen) histocompatibility antigens. The diagnostic criteria for celiac disease have undergone numerous modifications over the years. The aim of the study is to evaluate the frequency of HLA-DQ2/DQ8 genes in a group of patients with celiac disease diagnosed in 1980-2010 in order to verify the primary diagnosis of CD. The study group included 50 patients, 13 men and 37 women, who had been diagnosed with celiac disease many years ago based on histopathological criteria and improvement of health condition after receiving a gluten-free diet. The control group consisted of 31 healthy volunteers, 18 women and 13 men. All subjects underwent a genetic analysis assessing the presence of histocompatibility antigens HLA-DQ2.2, -DQ2.5, and -DQ8, along with the assessment of alleles encoding the α and β subunits of the antigens, according to European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines from 2020, using the EUROarray technique at EUROIMMUNE®. In the study group, 12 (24%) patients did not meet the genetic criteria. Among the remaining patients (Group 1) with celiac disease, the presence of HLA-DQ2.5 (50.0% vs. 9.68%; p < 0.01) and the co-occurrence of both alleles of HLA-DQ2 (31.6% vs. 6.45%; p < 0.05) were detected significantly more frequently than in the control group. Among patients with celiac disease, the prevalence of HLA-DQ8 was also slightly more frequent (13.2% vs. 3.23%; p > 0.05). Patients who did not meet the genetic criteria for celiac disease (Group 2) had a single string α-HLA-DQ2.5 significantly more often than control subjects (66.67% vs. 38.71%; p < 0.05). Among patients with celiac disease diagnosed before 2010, based on the 2020 ESPGHAN criteria, it is advisable to verify the previous diagnosis, taking into account genetic criteria.

Gray matter volume and asymmetry in Broca's and Wernicke's area homologs in chimpanzees (Pan troglodytes) using a probabilistic region of interest approach.

Broca's and Wernicke's areas are comprised of Brodmann areas 44, 45 and 22 in the human brain. Because of their roles in higher cognitive and linguistic function, there has been historical and contemporary interest in comparative studies on the morphology and cytoarchitectonic organization in Broca's and Wernicke's between primate species. One challenge to comparative morphological studies between human and nonhuman primates for Broca's and Wernicke's areas is the absence in homologous sulci used to define these regions. To address this limitation, we created probabilistic atlas maps of BA44, BA45 and BA22 based on previously reported cytoarchitectonic maps of these regions in chimpanzees. We then applied the maps to segmented gray matter volume to estimate gray matter within each region and hemisphere. Females were found to have significantly higher gray matter volumes for BA44 and BA45 compared males. Significant negative associations were found between age and gray matter volume for BA44 and BA45 but not BA22. Population-level asymmetries were found for BA44, BA45 and BA22 but there are some limitations in the interpretation of these findings. Lastly, using quantitative genetic analyses, we found significant heritability in the average gray matter volume for BA44 and BA45 but not BA22. The sex and age effects found in chimpanzees are consistent with previous studies in humans.