Genetic Basis Research Articles

Genetic underpinning of idiopathic pulmonary fibrosis: the role of mucin.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive scarring and reduced survival. The development of IPF is influenced by rare and common genetic variants, cigarette smoking, aging, and environmental exposures. Among the two dozen genetic contributors, the MUC5B promoter variant (rs35705950) is the dominant risk factor, increasing the risk of both familial and sporadic IPF and accounting for nearly 50% of the genetic predisposition to the disease. This review provides an expert perspective on the genetic underpinnings of IPF rather than a systematic analysis, emphasizing key insights into its genetic basis. The articles referenced in this review were identified through targeted searches in PubMed, Scopus, and Web of Science for studies published between 2000 and 2023, prioritizing influential research on the genetic factors contributing to IPF. Search terms included 'idiopathic pulmonary fibrosis,' 'genetics,' 'MUC5B,' 'telomere dysfunction,' and 'surfactant proteins.' The selection of studies was guided by the authors' expertise, focusing on the most relevant publications. The identification of genetic variants not only highlights the complexity of IPF but also offers potential for earlier diagnosis and personalized treatment strategies targeting specific genetic pathways, ultimately aiming to improve patient outcomes.

Causative Genes of Homologous Recombination Deficiency (HRD)-Related Breast Cancer and Specific Strategies at Present

Recently, homologous recombination deficiency (HRD) has become a new target for hereditary cancers. Molecular-based approaches for hereditary cancers in the clinical setting have been reviewed. In particular, the efficacy of the PARP inhibitor has been considered by several clinical trials for various kinds of hereditary cancers. This indicates that the PARP inhibitor can be effective for any kind of BRCA mutated cancers, regardless of the organ-specific cancer. Homologous recombination deficiency (HRD) has become a new target for hereditary cancers, indicating the necessity to confirm the status of HRD-related genes. ARID1A, ATM, ATRX, PALB2, BARD1, RAD51C and CHEK2 are known as HRD-related genes for which simultaneous examination as part of panel testing is more suitable. Both surgical and medical oncologists should learn the basis of genetics including HRD. An understanding of the basic mechanism of homologous repair recombination (HRR) in BRCA-related breast cancer is mandatory for all surgical or medical oncologists because PARP inhibitors may be effective for these cancers and a specific strategy of screening for non-cancers exists. The clinical behavior of each gene should be clarified based on a large-scale database in the future, or, in other words, on real-world data. Firstly, HRD-related genes should be examined when the hereditary nature of a cancer is placed in doubt after an examination of the relevant family history. Alternatively, HRD score examination is a solution by which to identify HRD-related genes at the first step. If lifetime risk is estimated at over 20%, an annual breast MRI is necessary for high-risk screening. However, there are limited data to show its benefit compared with BRCA. Therefore, a large-scale database, including clinical information and a long-term follow-up should be established, after which a periodical assessment is mandatory. The clinical behavior of each gene should be clarified based on a large-scale database, or, in other words, real-world data.

Characterizing the Genetic Basis for Inherited Retinal Disease: Lessons Learned From the Foundation Fighting Blindness Clinical Consortium's Gene Poll.

The Foundation Fighting Blindness (FFB) Consortium is a collaboration of 41 international clinical centers that manage patients affected with inherited retinal diseases (IRDs). The annual Consortium gene poll was initiated in 2020 to capture the genetic cause of disease in patients with IRD and associated clinical practices of Consortium sites. Data from the 2022 gene poll are reported here. In 2022, academic, private practice, and government ophthalmology clinics that are members of the Consortium centers were polled to identify per-case IRD genetic causality from a list of 387 syndromic and nonsyndromic IRD genes. The survey also assessed how genetic testing was obtained and clinical practices of the sites. Thirty centers responded and reported genetic data from 33,834 patients (27,561 families). Disease-causing variants were reported in 293 of 387 genes. The most common genetic etiologies were ABCA4 (17%), USH2A (9%), RPGR (6%), PRPH2 (5%), and RHO (4%). The top 100 genes accounted for the genetic cause of disease in 94.4% of patients. Two-thirds of the centers had at least one genetic counselor. In the 21 US sites, genetic testing was commonly obtained through sponsored programs (95%, FFB-My Retina Tracker Programs or Spark-ID Your IRD), whereas in the 9 non-US sites, genetic testing was commonly obtained using either patient- or public health system-funded testing pipelines. Clinical work-up of patients with IRD most commonly included updating history, eye examination, and optical coherence tomography. This report provides the largest assessment of genetic causality in the IRD patient population across multiple continents to date.

Genomics of liver abscesses in feedlot cattle.

The primary reason livers are condemned is due to abscesses, which are visible lesions detected on the liver during routine harvest of the animal. Condemned livers are deemed not fit for human consumption, and result in over $15M in lost income to the U.S. beef industry each year. Liver scoring is a 4-level measurement of abscess severity: 0 (no abscesses), A- (mild: 1-2 small abscesses), A (moderate: 2-4 active abscesses) and A+ (severe: 1 or more large, active abscesses). We quantified the degree to which known sources of variation, including genomic differences among animals, contribute to the incidence of liver abscesses in 1747 feedlot cattle fed a range of diets. Diets were grouped based on corn type (dry-rolled corn (DRC), high-moisture corn (HMC), DRC/HMC or steam-flaked Corn (SFC)) and byproduct (none, modified distillers grains plus solubles (MDGS), and Sweet Bran fed at 20%, 35% or 40%). A common set of SNP (n= 44,666) from the Illumina BovineSNP50 v2 and GGP Bovine 100K were used for genomic analyses. The posterior mean (posterior standard deviation) heritability estimate of liver score was 0.10 (0.05). Within-diet heritability estimates were not significantly different from zero but ranged from 0.02 (0.02) (MDGS) to 0.29 (0.32) (Sweet Bran fed at 35%). A BayesB Genome Wide Association Study with showed that liver score is a very polygenic trait with no large QTL segregating in this population. The genetic and phenotypic correlations of liver score with hot carcass weight, 12th rib fat, longissimus muscle area, or marbling score were not significantly different from zero. Results from the current study show that genomic selection for reduced liver score could be a useful tool to reduce the occurrence of liver abscesses in feedlot cattle, alongside current mitigation strategies; however, more data is needed to gain a better understanding of the genetic basis of liver score, as well as the relationship between liver score and other economically relevant traits, and potential genetic x diet interactions.

Genetic Basis of Seedling Root Traits in Common Wheat (Triticum aestivum L.) Identified by Genome-Wide Linkage Mapping

Common wheat production is significantly influenced by abiotic stresses. Identifying the genetic loci for seedling root traits and developing the available molecular markers are crucial for breeding high yielding and stable varieties. In this study, five wheat seedling root traits, including root length (RL), root surface area (RA), root volume (RV), number of root tips (RT), and root dry weight (RW), were measured in the Wp-072/Wp-119 recombinant inbred line (RIL) population. Genotyping was conducted for the RIL population and their parents using the wheat 90K single-nucleotide polymorphism (SNP) chip. In total, three quantitative trait loci (QTLs) for RL (QRL.gau-1DS, QRL.gau-1DL and QRL.gau-4AL), two QTLs for RA (QRA.gau-1D and QRA.gau-2DL), one locus for RV (QRV.gau-6AS), two loci for RW (QRW.gau-2DL and QRW.gau-2AS), and two loci for RT (QRT.gau-3AS and QRT.gau-6DL) were identified, with each explaining 4.5–8.4% of the phenotypic variances, respectively. Among these, QRT.gau-3AS, QRL.gau-4AL, and QRV.gau-6AS overlapped with the previous reports, whereas the other seven QTLs were novel. The favorable alleles of QRL.gau-1DS, QRL.gau-1DL, QRL.gau-4AL, QRA.gau-1D, QRW.gau-2AS, QRV.gau-6AS, QRT.gau-3AS, and QRT.gau-6DL were contributed by Wp-072, whereas the other two loci originated from Wp-119. Additionally, five kompetitive allele-specific PCR (KASP) markers, KASP-RL-1DL for RL, KASP-RA-1D and KASP-RA-2DL for RA, KASP-RW-2AS and KASP-RW-2DL for RW, were developed and validated successfully in 149 wheat accessions. Furthermore, seven candidate genes mainly for plant hormones were selected and validated by quantitative real-time PCR (qRT-PCR). This study provides new loci, new candidate genes, available KASP markers, and varieties for optimizing wheat root system architecture.

Development of a set of monosomic alien addition lines from Gossypium raimondii in Gossypium hirsutum toward breeding applications in cotton

BackgroundGossypium raimondii Ulbr is a diploid wild cotton (2n = 26, D5D5) that originated in west-central Peru of South America and possesses desirable characteristics that are absent in the Upland cotton G. hirsutum. Many beneficial genes were lost from G. hirsutum in the process of domestication, leading to a narrowed genetic base and greater vulnerability to biotic and abiotic stresses. This genetic base can be expanded through distant hybridization using the superior genes of G. raimondii.ResultsIn this study, putative hexaploid F1 plants of G. hirsutum - G. raimondii were generated by interspecific hybridization. Analysis of its mitotic metaphase plates revealed the presence of 78 chromosomes, with each of the six chromosome-specific fluorescence in situ hybridization (FISH) probes (3D5, 5D5, 6D5, 7D5, 9D5, and 10D5) of G. raimondii exhibiting bright and distinct signals on its respective pair of chromosomes. Then, the fertile hexaploid F1 plants were continuously backcrossed with G. hirsutum and a set of G. hirsutum - G. raimondii monosomic alien addition lines (MAALs) were developed using SSR markers in successive backcrosses and self-crossing from BC2F1 to BC4F2. These MAALs were confirmed by chromosome-specific anchored SSRs and FISH. This set of MAALs exhibited abundant variation in morphological traits, agronomic characteristics, yield, and fiber quality traits, as well as in drought and salt resistance at seedling stage. Notably, MAAL_9D5 and MAAL_10D5 demonstrated excellent fiber length (FL), fiber uniformity (FU), fiber strength (FS), micronaire value, and fiber elongation (FE); At seeding stage, MAAL_8D5, MAAL9D5, MAAL_10D5, MAAL_12D5, and MAAL_13D5 showed salt resistance potential; while MAAL_1D5, MAAL_3D5, MAAL_4D5, MAAL_7D5, MAAL_8D5, MAAL_12D5, and MAAL_13D5 exhibited drought resistance potential. These MAALs will provide important genetic bridge materials for gene transfer from G. raimondii as well as for the study of Gossypium species genomes and their evolution.ConclusionsA set of Gossypium hirsutum - Gossypium raimondii MAALs were developed and they showed abundant variation in morphological, agronomic, yield, and fiber quality traits, as well as in drought and salt resistance at seedling stage.

Inheritance of Northern Corn Leaf Blight Resistance in Advanced Generations of Maize (Zea mays L.)

Developing genetically resistant maize varieties to mitigate yield losses would reduce reliance on chemical control measures. This study underlines the substantial genetic variability and heritability of northern corn leaf blight (NCLB) resistance within a recombinant inbred line (RIL) population, highlighting the genetic basis of the trait. ANOVA revealed highly significant genetic variability among families at the 1% level, confirming the presence of sufficient variability for effective selection. The progression from F5 to F6 generations demonstrated the effectiveness of selection, as seen from reduced AUDPC scores in the F6 generation. A genetic gain of -7.74 and a heritability estimate of 48% further validated the success of selection based on lower AUDPC scores. The regression analysis supported by the significant positive correlation (r = 0.65) revealed a significant association between F5 selections and the F6 AUDPC scores, as seen from an R2 value of 0.42 and a moderate predictive slope of 0.52. These associations suggest that while selection is effective in predicting advanced-generation performance, the residual variability points to the need for incorporating additional genetic or environmental factors to improve predictive accuracy. These findings emphasize the predominance of genetic factors in NCLB resistance and the stability of resistance traits across the two generations, offering insights into the genetic control of the trait. By providing a solid foundation for breeding efforts targeting durable resistance, this study contributes to the development of maize varieties with enhanced NCLB resistance and supports sustainable agricultural practices.

Identified Candidate Genes of Semen Trait in Three Pig Breeds Through Weighted GWAS and Multi-Tissue Transcriptome Analysis

High-quality semen is an essential factor for the success of artificial insemination, and revealing the genetic structure of pig semen traits helps improve semen quality. This study aimed to identify candidate genes associated with semen traits in three pig breeds (Duroc, Landrace, and Yorkshire) through weighted GWAS and multi-tissue transcriptome analysis. In this study, to identify candidate genes associated with semen traits in Duroc, Landrace, and Yorkshire, we performed weighted GWAS in four traits (sperm motility, sperm progressive motility, sperm abnormality rate, and total sperm count) using 936 pigs and multi-tissue transcriptome analysis using 34 tissues RNA-seq data of 5457 pigs from FarmGTEx. It was found that 16, 9, and 12 significant SNPs associated with semen traits were identified in Duroc, Landrace, and Yorkshire, with corresponding 7, 5, and 7 candidate genes in these three breeds, respectively, which may be involved in mammal spermatogenesis, testicular function, and male fertility. Moreover, we not only found the same candidate gene DNAI2 as in previous studies but also found two new candidate genes PNLDC1 and RSPH3, which were identified simultaneously in both Landrace and Yorkshire. By integrating the GWAS and multi-tissue transcriptome analysis results, we found that candidate genes associated with semen traits of three pig breeds were highly expressed in the testis tissue. The three genotypes of rs320928244 had significant effects on the expression of the DYNLT1 gene in the testis tissue of Landrace. These results together showed that these candidate genes were mainly related to sperm motility defects. This study helps deepen the understanding of the genetic basis of semen traits and provides a theoretical foundation for improving the semen quality of Duroc, Landrace, and Yorkshire breeds.

A Robust and Comprehensive Study of the Molecular and Genetic Basis of Neurodevelopmental Delay in a Sample of 3244 Patients, Evaluated by Exome Analysis in a Latin Population

Background and Objectives: Neurodevelopmental disorders (NDDs), including developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and specific learning disorders, affect 15% of children and adolescents worldwide. Advances in next-generation sequencing, particularly whole exome sequencing (WES), have improved the understanding of NDD genetics. Methodology: This study analyzed 3244 patients undergoing WES (single, duo, trio analyses), with 1028 meeting inclusion criteria (67% male; aged 0–50 years). Results: Pathogenic (P) or likely pathogenic (LP) variants were identified in 190 patients, achieving a diagnostic yield of 13.4% (singleton), 14% (duo), and 21.2% (trio). A total of 207 P/LP variants were identified in NDD-associated genes: 38% were missense (48 de novo), 29% frameshift (26 de novo), 21% nonsense (14 de novo), 11% splicing site (14 de novo), and 1% inframe (1 de novo). De novo variants accounted for 49.8% of cases, with 86 novels de novo variants and 27 novel non de novo variants unreported in databases like ClinVar or scientific literature. Conclusions: This is the largest study on WES in Colombian children with NDDs and one of the largest in Latino populations. It highlights WES as a cost-effective first-tier diagnostic tool in low-income settings, reducing diagnostic timelines and improving clinical care. These findings underscore the feasibility of implementing WES in underserved populations and contribute significantly to understanding NDD genetics, identifying novel variants with potential for further research and clinical applications.

Genetic Parameter Estimates for Carcass and Meat Quality Traits and Their Genetic Associations With Sexual Precocity Indicator Traits in Nellore Cattle.

For developing beef cattle breeding programmes, it is essential to understand the genetic basis of economically relevant traits, such as carcass, meat quality and female sexual precocity. However, the direct selection of most of these traits is a challenge for producers because of the high cost and measurement difficulty. Genetic correlation estimates between carcass and meat quality traits obtained after slaughter and sexual precocity indicator traits in Nellore are limited in the literature. Thus, this study aimed to estimate genetic parameters for longissimus muscle area (LMA), backfat thickness (BF), hot carcass weight (HCW), shear force tenderness (SF), marbling score (MARB), intramuscular fat content (IMF), age at first calving (AFC), heifer pregnancy (HP) and scrotal circumference (SC) in Nellore cattle, using pedigree and genomic information. For this, data from 6910 young bulls with phenotypic information for carcass and meat traits, 230,682 for sexual precocity indicator traits, and 17,850 animals genotyped with or imputed to the Illumina Bovine HD BeadChip were used. The (co)variance components and genetic parameters were estimated considering BLUP and single-step GBLUP (ssGBLUP) models via Bayesian inference using the GIBBSF90+ software. The multi-trait animal model included additive and residual genetic effects as random; the fixed effects of contemporary group (for all traits) and date of analysis as classes (for BF, SF and MARB); and the linear effects of age at slaughter (all carcass and meat traits) and age at yearling (YW and SC) as covariates. Heritability estimates ranged from 0.13 to 0.34 for carcass and meat quality traits, and for SC, AFC and HP, were 0.33, 0.07 and 0.29, respectively. Favourable genetic correlations were estimated between YW-HCW (0.79 ± 0.03), YW-LMA (0.28 ± 0.05), YW-SC (0.35 ± 0.03), HCW-LMA (0.44 ± 0.05), HCW-SF (-0.22 ± 0.09), HCW-SC (0.19 ± 0.05), MARB-IMF (0.90 ± 0.07), SF-IMF (-0.20 ± 0.11), BF-MARB (0.29 ± 0.08), BF-IMF (0.22 ± 0.09), BF-AFC (-0.21 ± 0.07) and BF-HP (0.24 ± 0.10). In general, the correlations between carcass traits and those of meat quality were low to moderate. Additionally, carcass and meat quality traits did not exhibit strong genetic correlations with female precocity indicators. So, to achieve significant genetic advances in female sexual indicator traits, carcass composition and meat quality, these traits must compose selection indices for Nellore cattle.

Determination of damaging SNP’s in SHANK3 gene with in silico methods

BackgroundAsperger's syndrome, autism, and other neurodevelopmental diseases are all included under the general term autism spectrum disorder. The SHANK3 gene has a significant role in autism spectrum disorder; mutations in this gene are seen in roughly 1–2% of patients with both autism and intellectual disability. This genetic association provides insight concerning SHANK3's potential significance in the disorder's development. There is considerable evidence associating SHANK3 mutations to autism spectrum disorder; hence, it is worthwhile to investigate the underlying molecular genetic mechanisms of the disease.ResultsThis research uses in silico approaches such as SIFT, PolyPhen-2, I-Mutant 2.0, and Project HOPE to find harmful SNPs, which are the single nucleotide polymorphisms the most prevalent types of genetic variation in humans, in the SHANK3 gene. After the analysis, from the NCBI dbSNP database, 1535 missense SNPs in the SHANK3 gene were identified, with 54 classified as deleterious. Among these, 30 SNPs were confirmed damaging by both SIFT and PolyPhen-2, and 28 led to increased protein stability while two decreased it. In the presented research, effects on protein structure of this SNPs are discussed.ConclusionsThis in silico study improves our understanding of the complicated molecular changes associated with the SHANK3 gene and contributes to a more comprehensive understanding of the genetic landscape. By deepening our knowledge of the genetic basis and molecular pathways linked to SHANK3 mutations, our findings may offer direction for focused experimental validations and treatment strategies for autism spectrum disorder.

Chromosome-level genome assembly of Malus niedzwetzkyana, the mother of Rosybloom crabapple

Malus niedzwetzkyana (MN) is the mother of Rosybloom hybrids, ornamental crabapples with red and purple flowers. We present a high-quality chromosome-scale genome for MN with a size of 672.64 Mb, anchored to 17 chromosomes and with a high BUSCO completeness score of 98.6%, reaching the ‘gold standard’ level. Moreover, our assembly has captured 28 telomeres. A total of 43,813 protein-coding genes was annotated in the MN genome. The assembled high quality provides a valuable opportunity to enhance our understanding of the genetic basis of flower colour and other ornamental traits in crabapples, thereby advancing the field of genetics and breeding.

Assessing the impact of pedigree attributes on the validity of quantitative genetic parameter estimates.

Investigating the evolution of complex traits in nature requires accurate assessment of their genetic basis. Quantitative genetic (QG) modeling is frequently applied to estimate the additive genetic variance (VA) in traits, combining phenotypic and pedigree data from a sample of individuals. Whether reconstructed from social links or molecular markers, empirical pedigrees differ in completeness, genealogical error rates and other attributes that can impact QG estimation. Here we investigate this impact using human genealogical data for six French-Canadian (FC) populations originating from the same genetic founding source but differing in their pedigrees' attributes. First, we simulated phenotypic values along pedigrees and under different trait architecture and 'true' parameter values (e.g. VA). Then we fitted mixed effects 'animal' models to these simulated data, to assess how QG estimation was impacted by pedigree attributes. Our results show that pedigree size and depth were important determinants of the precision, but not accuracy, of genetic parameter estimates. In contrast, pedigree completeness and entropy, two attributes related to the density of genealogical links, were not clearly associated with the performance of parameter estimation. Noticeably, a slight increase in the genealogical error rate was sufficient to cause a detectable underestimation of VA. Including maternal genetic effects into the simulations lead to a slight underestimation of VA with pedigrees of smaller size and depth. Despite originating from the same genetic source, the six pedigrees yielded wide variations in QG estimates under identical conditions. These findings highlight the importance of sensitivity analyses in pedigree-based genetic studies on natural populations.

Impacts of Body Colour, Symbionts and Genomic Regions on the Pea Aphid Wing Plasticity Variation.

Adaptive phenotypic plasticity describes the phenomenon in which a single genotype can produce a variety of phenotypes that match their environments. Like any trait, plasticity is a phenotype that can exhibit variation, but despite the ecological importance of plasticity variation, little is known about its genetic basis. Here we use the pea aphid to investigate the genetic basis of wing plasticity variation. Previous reports have suggested an ecological association between body coloration and wing plasticity strength in the pea aphid, so we tested the hypothesis that the body colour determination locus (tor) associated with wing plasticity variation. We discover that there is no relationship between body colour and wing plasticity in natural populations or in a genetic mapping population. We also localise the tor locus to the third autosome, whereas it was previously thought to be on the first autosome, a finding that will be important for future studies of the locus. We find that the presence of the bacterial symbiont Regiella is associated with higher levels of wing plasticity. Genome-wide association analysis of wing plasticity variation did not reveal an impact of the tor locus, consistent with independence of body colour and wing plasticity. This analysis implicated one possible candidate gene-a Hox gene, abdominal-A-underlying wing plasticity variation, although SNPs do not reach the level of genome-wide significance and therefore will require further study. Our study highlights that plasticity variation is complex, impacted by a bacterial symbiont and genetic variation, but not influenced by body colour.

Heterochrony in orthodenticle expression is associated with ommatidial size variation between Drosophila species

BackgroundThe compound eyes of insects exhibit extensive variation in ommatidia number and size, which affects how they see and underlies adaptations in their vision to different environments and lifestyles. However, very little is known about the genetic and developmental bases of differences in eye size. We previously showed that the larger eyes of Drosophila mauritiana compared to D. simulans are generally caused by differences in ommatidia size rather than number. Furthermore, we identified an X-linked chromosomal region in D. mauritiana that results in larger eyes when introgressed into D. simulans.ResultsHere, we used a combination of fine-scale mapping and gene expression analysis to further investigate positional candidate genes on the X chromosome. We found earlier expression of orthodenticle (otd) during ommatidial maturation in D. mauritiana than in D. simulans, and we show that this gene is required for the correct organisation and size of ommatidia in D. melanogaster. We discovered that the activity of an otd eye enhancer is consistent with the difference in the expression of this gene between species, with the D. mauritiana enhancer sequence driving earlier expression than that of D. simulans. When otd expression is driven prematurely during D. melanogaster eye development, the ommatidia grow larger, supporting a possible role for the timing of otd expression in regulating ommatidial size. We also identified potential direct targets of Otd that are differentially expressed between D. mauritiana and D. simulans during ommatidial maturation.ConclusionsTaken together, our results suggest that differential timing of otd expression may contribute to natural variation in ommatidia size between D. mauritiana and D. simulans, which provides new insights into the mechanisms underlying the regulation and evolution of compound eye size in insects.

Kerry J. Ressler: Exploring the translation of amygdala function at the cellular and genomic levels to understand stress, fear, and trauma disorders, such as post-traumatic stress disorder (PTSD)

A pioneering force in psychiatric neuroscience, Dr. Kerry Ressler divides his time between serving as Chief Scientific Officer at McLean Hospital, Professor of Psychiatry at Harvard Medical School, and translational neuroscientist. Drawing from both molecular biology and human genetics, he has fundamentally changed how we understand fear and anxiety in the brain, especially through his innovative research on the amygdala. Throughout his remarkable career, which includes over 500 published papers, he has uncovered critical insights into the genetic and epigenetic basis of post-traumatic stress disorder (PTSD) and related anxiety disorders. His expertise has earned him membership in the National Academy of Medicine and a term as president of the Society for Biological Psychiatry. Dr. Ressler co-directs the Psychiatric Genomics Consortium PTSD Workgroup and founded the Grady Trauma Project in Atlanta before joining McLean Hospital. This Genomic Press Interview offers an intimate look at the path and perspectives of a scientist who has shaped modern psychiatric research and treatment.

Low-density SNP marker sets for genetic variation analysis and variety identification in cultivated citrus

BackgroundThe Citrus species are major fruit crops cultivated in the world and have complex genetic relationships due to sexual comparability between Citrus and related genera. Of these, satsuma mandarin (C. unshiu (Mak.) Marc.) and sweet orange (C. sinensis (L.) Osb.) are widely grown diploid species. In this study, genotyping by sequencing (GBS) was conducted to identify single nucleotide polymorphisms (SNPs) for investigating genetic variation in a citrus collection.ResultsA total of 26,903 high-quality SNPs were detected across nine chromosomes in the 144 citrus varieties, consisting of 70 C. unshiu, 40 C. sinensis, 22 interspecific hybrids, and 12 others. Of these, a core set of 481 SNPs was filtered based on polymorphism information content and genome distribution. Both principal component analysis (PCA) and model-based clustering showed genetic differentiation between C. unshiu and C. sinensis. For interspecific hybrids, these were separated from two species in PCA, but were mixed with each species in model-based clustering. Significant genetic differentiations between three populations were also found using the pairwise Fst. In addition, interspecific hybrids showed higher level of genetic diversity relative to the C. unshiu and C. sinensis populations. With the 481 SNPs, four subsets (192, 96, 48, and 24 SNPs) were generated to evaluate their performance for variety identification. Both 192 and 96 SNP sets distinguished all 144 varieties, while the 48 and 24 SNP sets separated 134 (93.1%) and 110 (76.4%), respectively.ConclusionsThe GBS-based SNP discovery led to robust and cost-effective molecular marker sets to assess genetic variation in the cultivated citrus species with narrow genetic bases. The resulting SNP sets are a resource to enhance the phenotype-based DUS testing by developing a DNA barcode system and thus facilitate new variety breeding and protection in citrus.

Pea aphid wing plasticity variation has a multigenic basis.

Phenotypic plasticity, the ability of a single genotype to produce a range of phenotypes in response to environmental cues, can exhibit genetic variation like any trait. Discovering the genetic basis of plasticity and plasticity variation is critical to understand how populations will respond to the ongoing environmental challenges brought about by, for example, climate change. Here, we investigate the genetic basis of the pea aphid (Acyrthosiphon pisum) wing plasticity variation. In this species, genetically identical, highly fecund wingless and dispersive winged individuals are produced by pea aphid mothers in uncrowded versus crowded environments, respectively. We focus specifically on the genetic basis of the propensity to produce winged individuals in response to crowding. We crossed a low to a high plasticity line and examined plasticity variation in backcross progeny (F1 x low parent), finding that differences between lines had a strong genetic component and that multiple loci likely to contribute to this variation. Transcriptional profiling revealed a candidate gene, yellow-h, which was found within a genomic locus contributing to plasticity variation. Overall, we provide novel information about the genetic basis of an ecologically-relevant trait and contribute to the growing literature recognizing the importance of understanding the genetic basis of plasticity variation.

Genotype-Based Molecular Mechanisms in Alport Syndrome

Abstract Alport syndrome (AS) is an inherited disorder characterized by kidney disease, sensorineural hearing loss and ocular abnormalities. AS is caused by pathogenic variants in COL4A3, COL4A4 or COL4A5, which encode the α3, α4 and α5 chains of type IV collagen that forms a heterotrimer expressed in the glomerular basement membrane. Knowledge of its genetic basis has informed the development of different models in dogs, mice and rat that reflect its autosomal and X-linked inheritance patterns as well as different mutation types, including protein truncating and missense variants. A key difference between these two types is the synthesis of α3α4α5(IV), which is not made in autosomal AS (2 pathogenic variants in trans or biallelic) or males with X-linked Alport syndrome due to protein truncating variants. By contrast, α3α4α5(IV) is synthesized in AS due to missense variants. For missense variants, in vitro studies suggest that these cause impaired type IV collagen trafficking and ER stress. For protein truncating variants, knockout models suggest that persistence of an immature α1α1α2(IV) network is associated with biomechanical strain, which activates endothelin-A receptors leading to mesangial filopodia formation. Moreoever, studies suggest that activation of collagen receptors integrins and DDR1 play a role in disease propagation. In this review, we provide an overview of how these genotype-phenotype-mechanisms are key for a precision medicine-based approach in the future.

Genetic architecture of cherry leaf spot (Blumeriella jaapii) resistance in sour cherry (P. Cerasus L.) uncovered by QTL analyses in a biparental population genotyped with the 6+9K SNP array

Abstract Sour cherry (Prunus cerasus L.) is an economically significant species in the Rosaceae family. Hitherto, there had been limited genetic and genomic resources to elucidate important horticultural traits in this species mainly because of the complex polyploid nature of its genome, a hybrid between Prunus avium and Prunus fruticosa. An important trait that has not been well studied in sour cherry is resistance to cherry leaf spot (CLS), caused by the fungus Blumeriella jaapii. This work took advantage of the RosBREED 6+9K SNP array to study the genetic basis of CLS resistance and inheritance in sour cherry. We established an F1 segregating population by crossing two cultivars, ‘Schattenmorelle’ and ‘Pc 2’ and genotyped both parents and the progeny with the cherry 6+9K SNP array and SSR markers. We evaluated both parents and progeny for resistance and susceptibility to CLS under field conditions. The applied marker systems facilitated the development of parental genetic maps, and the identification of two stable QTLs associated with CLS resistance, CLSR_1f in ‘Pc 2’ and susceptibility, CLSS_1f, in ‘Schattenmorelle’ explaining 40.9% and 21.5%, respectively of the phenotypic variation within the population. The mechanism of resistance in sour cherry appears to be independent of the CLS resistance QTL, CLSR_G4, previously identified in P. canescens, as the CLSR_G4-QTL and associated allele were not identified. Based on our findings, we propose a two-gene model for CLS resistance in sour cherry involving a susceptibility QTL, which might explain why some CLSR_G4-resistant plants in previous studies were susceptible.