Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been described.Case presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.Conclusions: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

SoySNP618K array:A high-resolution single nucleotide polymorphism platform as a valuable genomic resource for soybean genetics and breeding

Innovations in genomics have enabled the development of low-cost,high-resolution,single nucleotide polymorphism(SNP)genotyping arrays that accelerate breeding progress and support basic research in crop science.Here,we developed and validated the Soy SNP618 K array(618,888 SNPs)for the important crop soybean.The SNPs were selected from whole-genome resequencing data containing 2,214 diverse soybean accessions;29.34%of the SNPs mapped to genic regions representing 86.85%of the 56,044annotated high-confidence genes.Identity-by-state analyses of 318 soybeans revealed 17 redundant accessions,highlighting the potential of the Soy SNP618 K array in supporting gene bank management.The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data,suggesting that the ascertainment bias in the Soy SNP618 K array was largely compensated for.Genome-wide association mapping in combination with reported quantitative trait loci enabled fine-mapping of genes known to influence flowering time,E2 and Gm PRR3 b,and of a new candidate gene,Gm VIP5.Moreover,genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate(>0.65).Thus,the Soy SNP618 K array is a valuable genomic tool that can be used to address many questions in applied breeding,germplasm management,and basic crop research.

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,highthroughput 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.

Development of a 50K SNP Array for Japanese Flounder and Its Application in Genomic Selection for Disease Resistance

Single nucleotide polymorphism(SNP)armays are a powerful genotyping tool used in genetic research and genomic breeding programs.Japanese flounder(Paralichthys olivaceus)is an economically-important aquaculture flatfish in many countries.However,the lack of high-efficient genotyping tools has impeded the genomic breeding programs for Japanese flounder.We developed a 50K Japanese flounder SNP array,"Yuxin No.1,"and report its utility in genomic selection(GS)for disease resistance to bacterial pathogens.We screened more than 42,.2 million SNPs from the whole-genome resequencing data of 1099 individuals and selected 48697 SNPs that were evenly distributed across the genome to anchor the array with Affymetrix Axiom genotyping technology.Evaluation of the array performance with 168 fishs howed that 74.7%of the loci were successfully genotyped with high call rates(>98%)and that the poly-morphic SNPs had good cluster separations.More than 85%of the SNPs were concordant with SNPs obtained from the whole-genome resequencing data.To validate"Yuxin No.1"for GS,the arrayed geno-typing data of 27 individuals from a candidate population and 931 individuals from a reference popula-tion were used to calculate the genomic estimated breeding values(GEBVs)for disease resistance toEdwardsiella tarda.There was a 21.2%relative increase in the accuracy of GEBV using the weighted geno-mic best linear unpiased prediction(wGBLUJP),compared to traditional pedigree-based best linear unbi-ased prediction(ABLUP),suggesting good performance of the'Yuxin No.1"SNP array for GS.In summary,we developed the"Yuxin No.1"50K SNP array,which provides a useful platform for high-quality geno-typing that may be beneficial to the genomic selective breeding of Japanese flounder.

Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia with Chromothripsis in an Old Woman

Cell karyotyping in patients with small lymphocytic lymphoma/chronic lymphocytic leukemia （SLL/CLL） is not easy to success, and small genomic lesions （〈5 Mb） are not routinely detected by this method. It is likely that a complete genomic characterization of CLL requires a combination of fluorescence in situ hybridization （FISH）, single nucleotide polymorphism （SNP） array profiling for comprehensive genome-wide analysis of acquired genomic copy number aberrations （aCNAs） and loss-of-heterozygosity （LOH） in dominant clones, and karyotyping for detection of balanced translocations, isochromosomes, and marker chromosomes. SNP array analysis can reveal chromothripsis, a phenomenon by which regions of the cancer genome are shattered and recombined to generate frequent oscillations between the lower and the higher DNA copy number states. This study provided cytogenetic findings in a CLL/SLL patient with v-myc avian myelocytomatosis viral oncogene homolog （C-MYC）-amplification by FISH, in which SNP arrays detected profound genomic upheaval due to chromothripsis that may lead to malignant transformation.

A High-Density SNP Genotyping Array for Rice Biology and Molecular Breeding

A high-density single nucleotide polymorphism （SNP） array is critically important for geneticists and molecu- lar breeders. With the accumulation of huge amounts of genomic re-sequencing data and available technologies for accurate SNP detection, it is possible to design high-density and high-quality rice SNP arrays. Here we report the devel- opment of a high-density rice SNP array and its utility. SNP probes were designed by screening more than 10 000 000 SNP loci extracted from the re-sequencing data of 801 rice varieties and an array named RiceSNP50 was produced on the Illumina Infinium platform. The array contained 51 478 evenly distributed markers, 68% of which were within genic regions. Several hundred rice plants with parent/F1 relationships were used to generate a high-quality cluster file for accurate SNP calling. Application tests showed that this array had high genotyping accuracy, and could be used for dif- ferent objectives. For example, a core collection of elite rice varieties was clustered with fine resolution. Genome-wide association studies （GWAS） analysis correctly identified a characterized QTL. Further, this array was successfully used for variety verification and trait introgression. As an accurate high-throughput genotyping tool, RiceSNP50 will play an important role in both functional genomics studies and molecular breeding.