SNP Array Research Articles

Studies of genetic diversity and genome-wide association for vitamin C content in lettuce (Lactuca sativa L.) using high-throughput SNP arrays.

Lettuce (Lactuca sativa L.) is a source of beneficial compounds though they are generally present in low quantities. We used 40K Axiom and 9K Infinium SNP (single nucleotide polymorphism) arrays to (i) explore the genetic variability in 21 varieties and (ii) carry out genome-wide association studies (GWAS) of vitamin C content in21 varieties and a population of 205 plants from the richest variety in vitamin C ('Lechuga del Pirineo'). Structure and phylogenetic analyses showed that the group formed mainly by traditional varieties was the most diverse, whereas the red commercial varieties clustered together and very distinguishably apart from the rest. GWAS consistently detected, in a region of chromosome 2, several SNPs related to dehydroascorbic acid (a form of vitamin C) content using three different methods to assess population structure, subpopulation membership coefficients, multidimensional scaling, and principal component analysis. The latter detected the highest number of SNPs (17) and the most significantly associated, 12 of them showing a high linkage disequilibrium with the lead SNP. Among the 84 genes in the region, some have been reported to be related to vitamin C content or antioxidant status in other crops either directly, like those encoding long non-coding RNA, several F-box proteins, and a pectinesterase/pectinesterase inhibitor, or indirectly, like extensin-1-like protein and endoglucanase 2 genes. The involvement of other genes identified within the region in vitamin C levels needs to be further studied. Understanding the genetic control of such an important quality trait in lettuce becomes very relevant from a breeding perspective.

Genome-wide mapping of quantitative trait loci conferring resistance to stripe rust in spring wheat line PI 660072.

Two major QTL for resistance to stripe rust were mapped on chromosome 2BL and 4BL in spring wheat PI 660072, and their KASP markers were developed. Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of wheat worldwide. Identifying resistance genes is crucial for developing resistant cultivars to control the disease. Spring wheat PI 660072 (Triticum aestivum) has been identified to possess both adult-plant resistance (APR) and all-stage resistance (ASR) to stripe rust. To elucidate the genetic basis of the resistance in PI 660072, a mapping population consisting of 211 F5-F7 recombinant-inbred lines (RILs) was developed from a cross of PI 660072 with susceptible spring wheat Avocet S. The mapping population was phenotyped for stripe rust responses across five field environments from 2020 to 2022 and genotyped using the 15K SNP (single nucleotide polymorphism) array to map stripe rust resistance loci. The mapping population was also tested at the seedling stage with predominant Chinese Pst races CYR31, CYR32, CYR34 and PST-YX1-3-1 in the greenhouse. Stripe rust resistance genes were identified using the quantitative trait locus (QTL) mapping approach. Two QTL were identified with QYrPI660072.swust-2BL mapped on the long arm of chromosome 2B for ASR and QYrPI660072.swust-4BL on the long arm of chromosome 4B for APR. To facilitate marker-assisted selection breeding, Kompetitive allele specific PCR (KASP) markers, KASP-1269 for QYrPI660072.swust-2BL and KASP-3209 for QYrPI660072.swust-4BL, were developed. These markers could be used to introgress the effective resistance QTL into new wheat cultivars.

Advancing equine genomics: the development of a high density Axiom_Ashwa SNP chip for Indian horses and ponies.

The unique horse and pony breeds of India are declining at an alarming rate. These horses have been integral to the Indian culture and customs for centuries and represent a valuable genetic resource. It is imperative to harness the potential of this equine genetic resource that urgently needs conservation. The study highlights the design and development of a high density SNP array, the Axiom_Ashwa to aid in the genetic analysis and conservation efforts for Indian horse and pony breeds. With 613,950 SNPs, this chip offers extensive genome coverage having an average inter-marker distance of 4kb. The Axiom_Ashwa has been validated on a larger set of diverse indigenous samples as well as Thoroughbreds, demonstrating a high call rate of 99.4% and robustness for genotyping indigenous breeds. Linkage disequilibrium (LD) analysis showed higher average LD in Indian breeds compared to exotic breeds, suggesting a limited effective population size and recent bottlenecks. Phylogenetic and population stratification analyses using PCA and DAPC clearly distinguished horses, ponies and Thoroughbreds, confirming the efficacy of the Axiom_Ashwa chip. These findings underscore the urgent need for conservation efforts for Indian horse breeds, which have experienced significant drop in population size. The Axiom_Ashwa SNP chip offers advantages such as cost-effectiveness and high throughput, providing a more accurate genetic representation of Indian horses.

SMARTER-database: a tool to integrate SNP array datasets for sheep and goat breeds.

The code is available as open-source software under the MIT license at https://github.com/cnr-ibba/SMARTER-database.

Analysis of the winter oilseed rape recombination landscape suggests maternal-paternal bias.

Recombination, the reciprocal exchange of DNA between homologous chromosomes, is a mandatory step necessary for meiosis progression. Crossovers between homologous chromosomes generate new combinations of alleles and maintain genetic diversity. Due to genetic, epigenetic, and environmental factors, the recombination landscape is highly heterogeneous along the chromosomes and it also differs between populations and between sexes. Here, we investigated recombination characteristics across the 19 chromosomes of the model allopolyploid crop species oilseed rape (Brassica napus L.), using two unique multiparental populations derived from two genetically divergent founder pools, each of which comprised 50 genetically diverse founder accessions. A fully balanced, pairwise chain-crossing scheme was utilized to create each of the two populations. A total of 3213 individuals, spanning five successive generations, were genotyped using a 15K SNP array. We observed uneven distribution of recombination along chromosomes, with some genomic regions undergoing substantially more frequent recombination in both populations. In both populations, maternal recombination events were more frequent than paternal recombination. This study provides unique insight into the recombination landscape at chromosomal level and reveals a maternal-paternal bias for recombination number with implications for breeding.

Whole-genome sequencing study in Koreans identifies novel loci for Alzheimer's disease.

The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood. We performed an AD genome-wide association study using whole-genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single-nucleotide polymorphism array data from 2978 Japanese (1336 AD cases, 1642 controls). Significant findings were evaluated by pathway enrichment and differential gene expression analysis in brain tissue from controls and AD cases with and without dementia prior to death. We identified genome-wide significant associations with APOE in the total sample and ROCK2 (rs76484417, p=2.71×10-8) among APOE ε4 non-carriers. A study-wide significant association was found with aggregated rare variants in MICALL1 (MICAL like 1) (p=9.04×10-7). Several novel AD-associated genes, including ROCK2 and MICALL1, were differentially expressed in AD cases compared to controls (p<3.33×10-3). ROCK2 was also differentially expressed between AD cases with and without dementia (p=1.34×10-4). Our results provide insight into genetic mechanisms leading to AD and cognitive resilience in East Asians. Novel genome-wide significant associations for AD identified with ROCK2 and MICALL1. ROCK2 and MICALL1 are differentially expressed between AD cases and controls in the brain. This is the largest whole-genome-sequence study of AD in an East Asian population.

Genetic Variation and QTL Analysis of Crude Fibre and Quality Traits in the Doubled Haploid Winter Oilseed Rape (Brassica napus L.) Population R19 x Lord

ABSTRACTThe oil‐extracted meal of oilseed rape is used for feeding livestock and is a potential source of vegetable protein for human consumption. Its protein quality is limited by glucosinolates, phenolic compounds, phytates and crude fibres. The reduction of cellulose, hemicellulose and indigestible lignin in black‐seeded oilseed rape may enhance the protein content, colour, sensory quality and digestibility. The objective of this study was to analyse the inheritance of seed fibre components in relation to oil, protein and other quality traits in a DH population derived from the cross of low lignin lines R19 and cv. Lord. The population of 143 lines was tested in field experiments in six environments and was genotyped with Illumina 15K Brassica SNP chip. QTL and candidate genes were identified using the high‐quality long‐read reference genome of Express 617. Major QTL for fibre components were identified on chromosomes C01 and C03 with opposite additive and epistatic effects. Fibre QTL colocated with each other and QTL for seed colour, oil and protein. Epistatic effects were identified, which resulted in a further decrease of fibre content.

Yr29 combined with QYr.nwafu-4BL.3 confers durable resistance to stripe rust in wheat cultivar Jing 411.

The combination of a QTL on chromosome arm 4BL and Yr29 provides durable resistance with no significant yield penalty. Wheat stripe rust or yellow rust (YR), caused by Puccinia striiformis f. sp. tritici (Pst), causes substantial yield reductions globally, but losses can be minimized by using resistance genes. Chinese wheat cultivar Jing 411 (J411) has continued to display an acceptable level of adult-plant resistance (APR) to YR in varied field conditions since its release in the 1990s. A recombinant inbred line (RIL) population comprising 187 lines developed from a cross of J411 and Kenong 9204 (KN9204) was evaluated in multiple environments to identify genomic regions carrying genes for YR resistance. A total of five quantitative trait loci (QTL) on chromosome arm 1BL, 3BS, 4BL, 6BS, and 7BL from J411 and two QTL on 3DS and 7DL from KN9204 were detected using inclusive composite interval mapping with the wheat 660K SNP array. QYr.nwafu-1BL.5 and QYr.nwafu-4BL.3 from J411 were robust and showed similar effects in all environments. QYr.nwafu-1BL.5 was likely the pleiotropic gene of Yr29/Lr46. QYr.nwafu-4BL.3 was located within a 1.0cM interval delimited by KASP markers AX-111609222 and AX-89755491. Based on haplotype analysis, Yr29 and QYr.nwafu-4BL.3 were identified as genetic components of quantitative resistance in a number of wheat cultivars. Moreover, RILs with Yr29 and QYr.nwafu-4BL.3 individually or when combined showed higher resistance to YR in rust nurseries compared with RILs without them, and there was no negative effect of their presence on agronomic traits under rust-free conditions. These results suggest that effective polymerization strategy is important for breeding high yielding and durable resistance cultivars.

Genomic Exploration of Essential Hypertension in African-Brazilian Quilombo Populations: A Comprehensive Approach with Pedigree Analysis and Family-Based Association Studies.

Essential Hypertension (EH) is a global health issue. Despite extensive research, much of EH heritability remains unexplained. We investigated the genetic basis of EH in African-derived individuals from partially isolated quilombo populations in Vale do Ribeira (SP-Brazil). Samples from 431 individuals (167 affected, 261 unaffected, 3 unknown) were genotyped using a 650k SNP array. Estimated global ancestry proportions were 47% African, 36% European, and 16% Native American. We constructed six pedigrees using additional data from 673 individuals and created three non-overlapping SNP subpanels. We phased haplotypes and performed local ancestry analysis to account for admixture. Genome-wide linkage analysis (GWLA) and fine-mapping via family-based association studies (FBAS) were conducted, prioritizing EH-associated genes through systematic approach involving databases like PubMed, ClinVar, and GWAS Catalog. Linkage analysis identified 22 regions of interest (ROIs) with LOD scores ranging 1.45-3.03, encompassing 2363 genes. Fine-mapping (FBAS) identified 60 EH-related candidate genes and 117 suggestive/significant variants. Among these, 14 genes, including PHGDH , S100A10 , MFN2 , and RYR2 , were strongly related to hypertension harboring 29 suggestive/significant SNPs. Through a complementary approach - combining admixture-adjusted GWLA based on Markov chain Monte Carlo methods, FBAS on known and imputed data, and gene prioritizing - new loci, variants, and candidate genes were identified. These findings provide targets for future research, replication in other populations, facilitate personalized treatments, and improve public health towards African-derived underrepresented populations. Limitations include restricted SNP coverage, self-reported pedigree data, and lack of available EH genomic studies on admixed populations for independent validation, despite the performed genetic correlation analyses using summary statistics.

Parkinson’s families project: a UK-wide study of early onset and familial Parkinson’s disease

The Parkinson’s Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson’s disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤45 years and/or a family history of PD in up to third-degree relatives. Where possible, we also recruited affected and unaffected relatives. We analysed DNA samples with a combination of single nucleotide polymorphism (SNP) array genotyping, multiplex ligation-dependent probe amplification (MLPA), and whole-genome sequencing (WGS). We investigated the association between identified pathogenic mutations and demographic and clinical factors such as age at motor symptom onset, family history, motor symptoms (MDS-UPDRS) and cognitive performance (MoCA). We performed baseline genetic analysis in 718 families, of which 205 had sporadic early-onset PD (sEOPD), 113 had familial early-onset PD (fEOPD), and 400 had late-onset familial PD (fLOPD). 69 (9.6%) of these families carried pathogenic variants in known monogenic PD-related genes. The rate of a molecular diagnosis increased to 28.1% in PD with motor onset ≤35 years. We identified pathogenic variants in LRRK2 in 4.2% of families, and biallelic pathogenic variants in PRKN in 3.6% of families. We also identified two families with SNCA duplications and three families with a pathogenic repeat expansion in ATXN2, as well as single families with pathogenic variants in VCP, PINK1, PNPLA6, PLA2G6, SPG7, GCH1, and RAB32. An additional 73 (10.2%) families were carriers of at least one pathogenic or risk GBA1 variant. Most early-onset and familial PD cases do not have a known genetic cause, indicating that there are likely to be further monogenic causes for PD.

A major falling number locus on chromosome 4B governs resistance to pre-harvest sprouting in bread wheat line Soru#1

Pre-harvest sprouting (PHS) is a serious threat to wheat quality and occurs when maturing seeds on plants encounter substantial rain before harvest. In the present study, the genetics of PHS resistance were studied using a population of 131 recombinant inbred lines (RILs) from a cross between Soru#1 and Naxos. The population was genotyped with the Illumina 90 K and Axiom 35 K wheat SNP arrays and tested in field trials across two locations in Norway and one in China. Seed dormancy as a measure of sprouting damage was evaluated using germination index (GI) and falling number (FN). Days to heading, days to maturity, and plant height were also recorded to evaluate their potential impact on PHS. Thirteen PHS-related quantitative trait loci (QTL) were detected. The most consistent QTL for FN, contributed by Soru#1, on the long arm of chromosome 4B explained 10.0–19.2% of the phenotypic variation across trials. Other important PHS resistance QTL from Soru#1 detected on chromosome arms 2AL, 2BL, and 4BS, affected both GI and FN. Naxos carried favorable QTL alleles for PHS resistance on chromosome arm 4AS and the Phs1 allele on 4AL. The reduced height Rht-D1 and vernalization Vrn-A1 alleles were the major determinants of plant height and earliness; however, these traits had minimal impact on the genetic control of PHS resistance in this population. Thus, both parents contributed valuable alleles for improving PHS resistance in breeding programs.

Prenatal diagnosis and postnatal follow-up of 15 fetuses with 16p13.11 microduplication syndrome.

The clinical phenotypes of 16p13.11 microduplication syndrome have been extensively reported in previous studies, mostly about adults and children, with limited information available on fetal cases. This study aims to explore the genotype-phenotype correlation of fetuses with 16p13.11 microduplication syndrome and analyze the characteristics of prenatal diagnosis indications and provide clinical information for prenatal and postnatal genetic counseling. We conducted a retrospective analysis of 3,451 pregnant women who underwent invasive prenatal diagnosis for SNP array between January 2018 and December 2022 at the Jinan Maternal and Child Health Hospital. Descriptive statistical analysis was performed on the prenatal diagnosis indications, pedigree analysis, pregnancy outcomes and postnatal follow-up of 15 fetuses with 16p13.11 microduplication syndrome. SNP array revealed that 15 fetuses had duplications in the 16p13.11 region with varying prenatal diagnosis indications. Among the cases, 6/15 exhibited ultrasound abnormalities, 5/15 had abnormal chromosomal copy number variations as indicated by non-invasive prenatal testing (NIPT), one case involved advanced maternal age, and 3/15 had other abnormalities. 16p13.11 microduplication syndrome was closely related to ultrasound abnormalities, especially structural abnormalities and soft marker anomalies (abnormal ultrasonic soft indicators), while the indication of NIPT could improve the detection rate of copy number variations (CNVs) in this region. Only 7/15 fetuses underwent pedigree verification, with one case of de novo 16p13.11 microduplication, and the others inherited from one parent. Pregnancy was terminated in 2/15 cases and the outcome of one case is unknown due to loss to follow-up. Among the remaining cases, only one case exhibited a ventricular septal defect, while another presented with omphalocele. No other obvious abnormalities were reported postnatally. The prenatal phenotypes of fetuses with 16p13.11 microduplication were highly associated with ultrasound abnormalities but lacked specificity. Comprehensive genetic tracing, outcome analysis, and follow-up are essential for providing accurate prenatal and postnatal genetic counseling.

Reliable RNA-seq analysis from FFPE specimens as a means to accelerate cancer-related health disparities research.

Whole transcriptome sequencing (WTS/ RNA-Seq) is a ubiquitous tool for investigating cancer biology. RNA isolated from frozen sources limits possible studies for analysis of associations with phenotypes or clinical variables requiring long-term follow-up. Although good correlations are reported in RNA-Seq data from paired frozen and formalin fixed paraffin embedded (FFPE) samples, uncertainties regarding RNA quality, methods of extraction, and data reliability are hurdles to utilization of archival samples. We compared three different platforms for performing RNA-seq using archival FFPE oropharyngeal squamous carcinoma (OPSCC) specimens stored up to 20 years, as part of an investigation of transcriptional profiles related to health disparities. We developed guidelines to purify DNA and RNA from FFPE tissue and perform downstream RNA-seq and DNA SNP arrays. RNA was extracted from 150 specimens, with an average yield of 401.8 ng/cm 2 of tissue. Most samples yielded sufficient RNA reads >13,000 protein coding genes which could be used to differentiate HPV-associated from HPV-independent OPSCCs. Co-isolated DNA was used to identify patient ancestry. Utilizing the methods described in this study provides a robust, reliable, and standardized means of DNA & RNA extraction from FFPE as well as a means by which to assure the quality of the data generated.

Identification of genetic loci for powdery mildew resistance in common wheat.

Powdery mildew (PM) poses an extreme threat to wheat yields and quality. In this study, 262 recombinant inbred lines (RILs) of Doumai and Shi 4185 cross were used to map PM resistance genes across four environments. High-density genetic linkage map of the Doumai/Shi 4185 RIL population was constructed using the wheat Illumina iSelect 90K single-nucleotide polymorphism (SNP) array. In total, four stable quantitative trait loci (QTLs) for PM resistance, QPm.caas-2AS, QPm.caas-4AS, QPm.caas-4BL, and QPm.caas-6BS, were detected and explained 5.6%-15.6% of the phenotypic variances. Doumai contributed all the resistance alleles of QPm.caas-2AS, QPm.caas-4AS, QPm.caas-4BL, and QPm.caas-6BS. Among these, QPm.caas-4AS and QPm.caas-6BS overlapped with the previously reported loci, whereas QPm.caas-2AS and QPm.caas-4BL are potentially novel. In addition, six high-confidence genes encoding the NBS-LRR-like resistance protein, disease resistance protein family, and calcium/calmodulin-dependent serine/threonine-kinase were selected as the candidate genes for PM resistance. Three kompetitive allele-specific PCR (KASP) markers, Kasp_PMR_2AS for QPm.caas-2AS, Kasp_PMR_4BL for QPm.caas-4BL, and Kasp_PMR_6BS for QPm.caas-6BS, were developed, and their genetic effects were validated in a natural population including 100 cultivars. These findings will offer valuable QTLs and available KASP markers to enhance wheat marker-assisted breeding for PM resistance.

Qtl Mapping for Grain Yield Component Traits in Recombinant Inbred Line Population of Bread Wheat Under Heat Stress Using 35 K Snp Array

Qtl Mapping for Grain Yield Component Traits in Recombinant Inbred Line Population of Bread Wheat Under Heat Stress Using 35 K Snp Array

Analyses of whole-genome sequences from 185 North American Thoroughbred horses, spanning 5 generations

Whole genome sequences (WGS) of 185 North American Thoroughbred horses were compared to quantify the number and frequency of variants, diversity of mitotypes, and autosomal runs of homozygosity (ROH). Of the samples, 82 horses were born between 1965 and 1986 (Group 1); the remaining 103, selected to maximize pedigree diversity, were born between 2000 and 2020 (Group 2). Over 14.3 million autosomal variants were identified with 4.5–5.0 million found per horse. Mitochondrial sequences associated the North American Thoroughbreds with 9 of 17 clades previously identified among diverse breeds. Individual coefficients of inbreeding, estimated from ROH, averaged 0.266 (Group 1) and 0.283 (Group 2). When SNP arrays were simulated using subsets of WGS markers, the arrays over-estimated lengths of ROH. WGS-based estimates of inbreeding were highly correlated (r > 0.98) with SNP array-based estimates, but only moderately correlated (r = 0.40) with inbreeding based on 5-generation pedigrees. On average, Group 1 horses had more heterozygous variants (P < 0.001), more total variants (P < 0.001), and lower individual inbreeding (FROH; P < 0.001) than horses in Group 2. However, the distribution of numbers of variants, allele frequency, and extent of ROH overlapped among all horses such that it was not possible to identify the group of origin of any single horse using these measures. Consequently, the Thoroughbred population would be better monitored by investigating changes in specific variants, rather than relying on broad measures of diversity. The WGS for these 185 horses is publicly available for comparison to other populations and as a foundation for modeling changes in population structure, breeding practices, or the appearance of deleterious variants.

B-203 Advancing Equity, Inclusion, and Diversity in Genetic Testing: Disparities in Detection Rates and Access to Carrier Screening Among 8,000 Patients Nationwide

Abstract Background Professional medical societies recommend that carrier screening for 113 different genetic disorders be offered during pregnancy or preconception to all individuals, regardless of ancestry, in order to provide more equitable opportunities for patients to ascertain their reproductive risks. In our clinical laboratory experience, however, the vast majority of healthcare providers continue to order carrier screening for only cystic fibrosis (CF), which is disproportionately common in white individuals of Northern European descent. Our highest volume CF screening test is performed on &amp;gt;10,500 diverse patients per year and utilizes a targeted genotyping array that detects &amp;gt;500 variants in CFTR and &amp;gt;1200 variants in &amp;gt;150 other pertinent genes. Here we report the inequities in diagnostic yield among our first 8,000 patients for whom only limited testing was ordered and examine the barriers to widespread adoption of more inclusive carrier screening. Methods Three carrier screening options (CF, CF+spinal muscular atrophy [SMA], CF+SMA+fragile X syndrome [FXS]+hemoglobinopathies) were ordered clinically and performed on DNA extracted from 8,000 whole blood samples from unique individuals utilizing a custom SNP array (Thermo Fisher GeneTitanTM platform) designed to detect &amp;gt;1700 pathogenic variants in 218 different genes. Data was retrospectively reviewed to determine overall detection rates for carriers of all recommended conditions vs. only the condition(s) included in the originally ordered service. Finally, reproductive health providers at nine different ordering sites across the U.S. were interviewed regarding their current carrier screening practices. Results Patients were referred for testing by 119 different clinical facilities. 98.1% (7847/8000) had CF-only testing ordered, 1.2% (99/8000) had CF+SMA testing ordered, and 0.68% (54/8000) had testing for CF+SMA+FXS+hemoglobinopathies ordered. 7.1% (568/8000) of patients had reportable variants in CFTR. Had CF+SMA testing been ordered on all 8,000 patients, however, the diagnostic yield would have been 8.9%. Of the patients who had CF-only or CF+SMA testing ordered, 11.9% (943/7946) were found to be carriers of hemoglobinopathies. Finally, had all 8000 patients had testing for all currently recommended targets on the panel, the diagnostic yield would have increased to 55% (4396/8000). Ordering providers at 9/50 different contacted sites agreed to interview requests. 100% (9/9) of respondents indicated that their patients experience significant disparities in access to carrier screening, and that the primary cause of these inequities was insufficient insurance reimbursement. 67% (6/9) of respondents indicated that &amp;gt;50% of their patient population identified as non-white and would have “very strongly” benefitted from “testing for other disorders beyond CF.” Conclusions Despite clinical practice guidelines urging for more population-neutral carrier screening, major gaps exist between what is recommended versus ultimately ordered. This significantly limits the clinical utility of testing, especially in patients from underrepresented backgrounds. Improved insurance coverage for more inclusive carrier screening is needed to help reduce such disparities.

Genomeprofile: Unveiling the genomic profile for livestock breeding through comprehensive SNP array-based genotyping.

In livestock breeding, single nucleotide polymorphism arrays have become a cornerstone of modern livestock breeding. SNP arrays facilitate the identification of genetic markers linked to economically important traits and provide a powerful tool for predicting breeding values. However, conventional breeding programs often overlook additional genomic features contained in the SNP array data that can provide valuable insights into the genetic diversity, copy number variation, inbreeding levels and potential challenges in breeding lines. Here we present genomeprofile, a tool using SNP array-based genomic data, offering a comprehensive profile of breeding animals including the identification of copy number variants and runs of homozygosity, and screening for aneuploidy. By integrating these features into the breeding landscape, genomeprofile enables a more comprehensive picture of genomic variation, ultimately enhancing precision breeding strategies. To illustrate the practicality and efficacy of genomeprofile, we applied the tool to a dataset of four pig breeding lines. The genomeprofile tool is a user-friendly tool that processes genotype data in finalreport or plink ped format efficiently into useful output. The output contains copy number variations, runs of homozygosity, selection signatures, aneuploidy and inbreeding per individual and across populations. This allows breeding companies and researchers to identify unique individuals or regions in the genome of interest based on routinely collected data.

Copy Number Variants in 30 Saudi Pediatric Patients with Neurodevelopmental Disorders: From Unknown Significance to Diagnosis.

Structural variants (SVs), such as copy number variants (CNVs), insertions, deletions, inversions, and translocations, contribute significantly to genetic diversity and disease etiology. CNVs, which involve the duplication or deletion of DNA segments, are particularly impactful on genes crucial for biological functions and disease processes. To reassess unclassified SVs that may be underlying unresolved neurodevelopmental disorders among Saudi patients. In this retrospective study conducted at King Saud Medical City, Riyadh, Saudi Arabia, 30 probands with neurodevelopmental disorders and congenital malformations were examined using next-generation sequencing methods-exome sequencing, gene panels, or SNP arrays (the Illumina platform). Reclassification was aided by online tools such as VarSome and ClinVar, with pathogenicity assessments using the ClinGen CNV Pathogenicity Calculator based on American College of Medical Genetics and Genomics criteria for CNV loss and gain, and dosage sensitivity. A total of 31 CNVs were analyzed, of which 2 were reclassified: one as benign and the other as pathogenic. The pathogenic CNV, [3p13p12.3 (70411134_75249376) x1], included a deletion of the FOXP1 gene and was associated with an intellectual developmental disorder, language impairment, possible autistic features, psychomotor impairment, developmental regression, and epilepsy. This study underscores the importance of continuously documenting and revisiting unclassified CNVs in accessible databases to enhance the diagnosis and understanding of complex genotype-phenotype relationships. Reclassifying these CNVs not only accelerates diagnostic processes but also enriches our insight into their significant roles in health and disease.

Development of a MaizeGerm50K array and application to maize genetic studies and breeding

Genotyping arrays based on single nucleotide polymorphisms (SNPs) provide a low-cost, high-throughput platform. The development of a SNP array that fully reflects the genetic diversity of maize (Zea mays L.) germplasm and is applicable to molecular breeding programs is desirable. In this study, we developed a MaizeGerm50K array comprising 50,852 SNPs selected from the resequencing data of 1604 maize inbred lines and other markers. A genome-wide association study using a landrace panel genotyped with the array permitted mapping of several known genes. We also verified a candidate gene, RNA-binding motif protein 24-like 1 (ZmRBM24L1), delaying flowering through overexpression lines. Genomic selection for yield and agronomic traits showed high prediction accuracy. The MaizeGerm50K array is thus a valuable genomic tool for maize genetic studies and breeding.