Hereditary white matter disease is a series of progressive genetic diseases that mainly affect the white matter of the central nervous system. The development of molecular genetics enables the clinical diagnosis, carrier detection, and prenatal diagnosis of hereditary white matter disease. Here, we block the transmission of pathogenic variants in ABCD1 and NOTCH3 in a family with cerebral white matter disease via preimplantation genetic testing (PGT). Pathogenic genes were identified based on clinical manifestations, genetic background, and the results of targeted gene capture sequencing. A blastocyst biopsy was performed, and multiple annealing and looping-based amplification (MALBAC), next-generation sequencing (NGS), and single nucleotide polymorphism (SNP) arrays were used to analyze ploidy and the state of the gene mutations. The proband (III:1) had hemizygous mutations in ABCD1 (c.323C>A (p.Ser108 *) and c.775C>T (p.Arg259Trp)) and heterozygous mutations in NOTCH3 (c.1630C>T (p.Arg544Cys)), which were maternally inherited (II:2). After genetic analysis, a euploid blastocyst without ABCD1 and NOTCH3 variations was transferred. A healthy male baby was born at full term, and the results of prenatal diagnosis by amniocentesis in the second trimester verified the results of PGT. To our knowledge, this is the first report of simultaneously blocking the transmission of pathogenic variants in ABCD1 and NOTCH3 via PGT. This report highlights the feasibility and effectiveness of PGT in preventing cerebral adrenoleukodystrophy (cALD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and provides valuable insights for the diagnosis and treatment of similar cases.

In patients with proximal hypospadias, often no genetic cause is identified despite extensive genetic testing. Many genes involved in sex development encode transcription factors with strict timing and dosing of the gene products. We hypothesised that there might be recurrent differences in DNA methylation in boys with hypospadias and that these might differ between patients born small versus appropriate for gestational age. Genome-wide Methylated DNA sequencing (MeD-seq) was performed on 32bp LpnPI restriction enzyme fragments after RE-digestion in leucocytes from 16 XY boys with unexplained proximal hypospadias, one with an unexplained XX testicular disorder/difference of sex development (DSD) and twelve, healthy, sex- and age-matched controls. Five of seven differentially methylated regions (DMRs) between patients and XY controls were in the Long Intergenic Non-Protein Coding RNA 665 (LINC00665; CpG24525). Three patients showed hypermethylation of MAP3K1. Finally, no DMRs in XX testicular DSD associated genes were identified in the XX boy versus XX controls. In conclusion, we observed no recognizable epigenetic signature in 16 boys with XY proximal hypospadias and no difference between children born small versus appropriate for gestational age. Comparison to previous methylation studies in individuals with hypospadias did not show consistent findings, possibly due to the use of different inclusion criteria, tissues and methods.

Homologous recombination plays pivotal roles in physical attachments and genetic diversity. In the past, it was studied among individuals from different populations. However, only few gametes from individual could generate offspring, which limits its exploration in nature selection. In the last few years, preimplantation blastocysts based on trio SNP-chip data were available in individuals for preimplantation genetic testing (PGT). In this protocol, we demonstrate how to detect meiotic recombination events and construct the genetic map based on trio SNP-chip data, obtained from biopsied blastocysts and their related individuals in PGT cycles, which may allow better understanding of recombination events in nature selection.

Uniparental disomies (UPD) refers to the inheritance of both homologs of a chromosome from only one parent with no representative copy from the other parent. UPD was with an estimated prevalence of 0.15‰ in population. Current understanding of UPD was limited to subjects for which UPD was associated with clinical manifestation due to imprinting disorders or recessive diseases. Segmental UPD was rare, especially for a segmental UPD with a combination of hetero- and isodisomy. This paper presents a couple with reciprocal translocation 46,XY, t(14;22)(q32.3;q12.2) for PGT-SR. Among 8 biopsied blastocysts, one euploid blastocyst (No.4) with segmental loss of heterozygosity (LOH)(22) [arr[hg19] q12.1q22.3 (28,160,407 - 35,407,682)] was detected by B allele frequency. We found the chromosome contained both UPiD(22) [arr[hg19] q12.1q22.3 (28,160,407 - 35,407,682) ×2 hmz mat] and UPhD(22) [arr[hg19] q22.3qter(35,407,682 - 51,169,045) ×2 htz mat] by haplotype analysis. UPDtool software confirmed the result. What\'s more, the segmental UPD and reciprocal translocation shared the same breakpoint, chr22q12.1 (28,160,407), while the breakpoint between iso- and heterodisomy was chr22q22.3 (35,407,682). We reported the first segmental UPD with a combination of hetero- and isodisomy, which may result from aneuploidy rescue. This case emphasizes the importance of the combination of comprehensive chromosome screening and haplotype analysis to reduce the risk of misdiagnosis.

Mullerian adenosarcoma is a rare malignant biphasic tumor. The mesenchymal component may be low or high grade, with or without sarcomatous overgrowth (SO). Little is known about the molecular heterogeneity of these tumors. In this study, we aim to reclassify a large retrospective monocentric cohort of uterine adenosarcomas according to tumor grade and SO, to evaluate the clinical significance of pathological classification and to correlate with copy-number variations inferred from single nucleotide polymorphism array. Of the 67 uterine adenosarcomas, 18 (26.9%) were low grade without SO, 7 (10.4%) low grade with SO, 8 (11.9%) high grade without SO and 34 (50.7%) high grade with SO. SO, necrosis and RMS were more frequent in high grade than low grade adenosarcomas (p < 0.001). Low-rank test showed that recurrence-free survival was significantly shortened in high grade than low grade adenosarcomas (p = 0.035) and SO was associated with shortened overall and recurrence-free survival (p = 0.038 and p = 0.009, respectively). High-grade tumors displayed complex genomic profiles with multiple segmental losses including TP53, ATM and PTEN genes. The median genomic index was significantly higher in high grade than low grade tumors (27 [3-60] vs 5,3 [0-16], p < 0.0001) and was significantly higher in presence of SO in low grade tumors (12,8 [10-16] vs 2,6 [0-10], p = 0.0006). We propose to report sarcomatous overgrowth with the tumor grade for prognostication in adenosarcoma and representative sampling is crucial for evaluation of these histological criteria.

BACKGROUND: Pre-implantation genetic testing for monogenic disorders (PGT-M) is an effective approach to reducing the incidence of birth defects by preventing the transmission of inherited diseases to offspring. However, there are still controversies regarding the detection methods and transplantation of embryos. This paper aims to evaluate the effectiveness of different detection technologies applied to PGT-M through a retrospective analysis of clinical detection data.
METHODS: The carrier status of pathogenic mutations and chromosomal copy number variants (CNVs) in 892 embryos was characterized using next-generation sequencing (NGS), single-nucleotide polymorphism (SNP) array, and PCR-based detection technologies. Clinical data from PGT-M cases were retrospectively analyzed to assess the effectiveness of these detection methods in identifying genetic abnormalities in embryos.
RESULTS: A total of 829 embryos were analyzed, with 63 being unsuccessful. Our study revealed that the success rate of detecting deletional mutations using Gap-PCR 84.9%, which is lower than that of SNP array (98.7%) and NGS (92.5%). However, no significant difference was observed when detecting point mutations using any of the methods. These findings suggest that, when detecting deletional mutations, SNP array and NGS are more suitable choices compared to Gap-PCR. While SNP array may have a lower resolution and success rate (80.5%) in analyzing CNVs compared to NGS (95.5%), it may still be useful for revealing certain abnormal types.
CONCLUSIONS: In conclusion, this study found that SNP analysis is advantageous for identifying polygenic and deletional mutations, whereas NGS is more cost-efficient for detecting common monogenic diseases. Additionally, SNP-based haplotyping and PCR-based direct detection of mutations can be used together to enhance the accuracy and success rates of PGT-M. Our findings offer valuable insights for PGT technicians in choosing suitable detection methods for patients.

The advances in genomics in recent years have increased the accuracy and efficiency of breeding programs for many crops. Nevertheless, the adoption of genomic enhancement for several other crops essential in developing countries is still limited, especially for those that do not have a reference genome. These crops are more often called orphans. This is the first report to show how the results provided by different platforms, including the use of a simulated genome, called the mock genome, can generate in population structure and genetic diversity studies, especially when the intention is to use this information to support the formation of heterotic groups, choice of testers, and genomic prediction of single crosses. For that, we used a method to assemble a reference genome to perform the single-nucleotide polymorphism (SNP) calling without needing an external genome. Thus, we compared the analysis results using the mock genome with the standard approaches (array and genotyping-by-sequencing (GBS)). The results showed that the GBS-Mock presented similar results to the standard methods of genetic diversity studies, division of heterotic groups, the definition of testers, and genomic prediction. These results showed that a mock genome constructed from the population\'s intrinsic polymorphisms to perform the SNP calling is an effective alternative for conducting genomic studies of this nature in orphan crops, especially those that do not have a reference genome.

OBJECTIVE: To evaluate the distribution of chromosomal abnormalities in a recurrent pregnancy loss (RPL) cohort and explore the associations between chromosomal abnormalities and clinical characteristics.
METHODS: Over a 5-year period, fresh products of conception (POC) from women with RPL were analyzed by single-nucleotide polymorphism (SNP) array at our hospital. After obtaining the information on clinical characteristics, we investigated the associations between the causative chromosomal abnormalities and clinical characteristics by the chi-squared test or Fisher\'s exact test and logistic regression.
RESULTS: A total of 2383 cases were enrolled. Overall, 56.9% (1355/2383) were identified with causative chromosomal abnormalities, of which 92.1% (1248/1355) were numerical abnormalities, 7.5% (102/1355) were structural variants, and 0.4% (5/1355) were loss of heterozygosity (LOH). The risk of numerical abnormalities was increased in women with maternal age ≥ 35 years (OR, 1.71; 95% CI, 1.41-2.07), gestational age at pregnancy loss ≤ 12 weeks (OR, 2.78; 95% CI, 1.79-4.33), less number of previous pregnancy losses (twice: OR, 2.32; 95% CI, 1.84-2.94; 3 times: OR, 1.59; 95% CI, 1.23-2.05, respectively), and pregnancy with a female fetus (OR, 1.37; 95% CI, 1.15-1.62). The OR of pregnancy loss with recurrent abnormal CMA was 4.00 (95% CI: 1.87-8.58, P < 0.001) and the adjusted OR was 5.05 (95% CI: 2.00-12.72, P = 0.001). However, the mode of conception was not associated with the incidence of numerical abnormality. No association was noted between structural variants and clinical characteristics.
CONCLUSIONS: Chromosomal abnormality was the leading cause of RPL. Numerical chromosome abnormality was more likely to occur in cases with advanced maternal age, an earlier gestational age, fewer previous pregnancy losses, and pregnancy with a female fetus.

UNASSIGNED: To share our experience on prenatal diagnosis of Williams-Beuren syndrome(WBS) and to improve the awareness, diagnosis, and intrauterine monitoring of the fetuses of this disease.
UNASSIGNED: The study retrospectively evaluated 14 cases of WBS diagnosed prenatally by single nucleotide polymorphism array (SNP-array). Clinical data from these cases were systematically reviewed, including maternal demographics, indications for invasive prenatal diagnosis, ultrasound findings, SNP-array results, trio-medical exome sequencing (Trio-MES) results, QF-PCR results, pregnancy outcomes and follow-ups.
UNASSIGNED: A total of 14 fetuses were diagnosed with WBS and their prenatal phenotypes were assessed retrospectively. In our case series, the most common ultrasound features were intrauterine growth retardation (IUGR), congenital cardiovascular defects, abnormal fetal placental doppler indices, thickened nuchal translucency(NT) and polyhydramnios. Other less common ultrasound features include fetal hydrops, hydroderma, bilateral pleural effusion, subependymal cysts, etc. Parental chromosome analysis was performed in seven pairs of parents, and all the deletions on chromosome 7q11.23 were de novo.
UNASSIGNED: Prenatal ultrasound features of WBS cases are highly variable, with IUGR, cardiovascular abnormalities and abnormal fetal placental doppler indices, being the most common intrauterine phenotypes. Our case series expand the intrauterine phenotypes of WBS, including cardiovascular abnormalities right aortic arch(RAA) combined with persistent right umbilical vein(PRUV) and elevated the ratio of end-systolic peak flow velocity to end-diastonic peak flow velocity(S/D). In the meantime, with the decrease in the cost of the next-generation sequencing, the method may become widely used in prenatal diagnosis in the near future.

Introducing the SNP technology to pigeon breeding will enhance the competitiveness of a sector that produces one of the healthiest and best quality meats. The present study aimed to test the applicability of the Illumina Chicken_50K_CobbCons array on 24 domestic pigeon individuals from the Mirthys hybrids and Racing pigeon breeds. A total of 53,313 SNPs were genotyped. Principal component analysis shows a significant overlap between the two groups. The chip performed poorly in this data set, with a call rate per sample of 0.474 (49%). The low call rate was likely due to an increase in the evolutionary distance. A total of 356 SNPs were retained after a relatively strict quality control. We have demonstrated that it is technically feasible to use a chicken microarray chip on pigeon samples. Presumably, with a larger sample size and by assigning phenotypic data, efficiency would be improved, allowing more thorough analyses, such as genome-wide association studies.