scholarly journals Molecular characterization of the Yp11.2 region deletion in the Chinese Han population

2021 ◽  
Author(s):  
Qianqian Pang ◽  
Qingai Lin ◽  
Di Wang ◽  
Zhenghao Sun ◽  
Junfang Wang
Keyword(s):  
Y Chromosome ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Tandem Repeats ◽  
Population Based ◽  
Chinese Han ◽  
Specific Sequence ◽  
Sequence Tagged Sites ◽  
Deletion Pattern ◽  
Male Specific

AbstractThe Y chromosome is male-specific and is important for spermatogenesis and male fertility. However, the Y chromosome is poorly characterized due to massive palindromes and inverted repeats, which increase the likelihood of genomic rearrangements, resulting in short tandem repeats on the Y chromosome or long fragment deletions. The present study reports a large-scale (2.573~2.648 Mb) deletion in the Yp11.2 region in a Chinese population based on the analysis of 34 selected Y-specific sequence-tagged sites and subsequent sequencing of the breakpoint junctions on the Y chromosome from 5,068,482–5,142,391 bp to 7,715,462–7,716,695 bp. The results of sequence analysis indicated that the deleted region included part or all of the following five genes: PCDH11Y, TSPY, AMELY, TBL1Y, and RKY. These genes are associated with spermatogenesis or amelogenesis and various other processes; however, specific physiological functions and molecular mechanisms of these genes remain unclear. Notably, individuals with this deletion pattern did not have an obvious pathological phenotype but manifested some degree of amelogenesis imperfecta.

scholarly journals CSYseq: The first Y-chromosome sequencing tool typing a large number of Y-SNPs and Y-STRs to unravel worldwide human population genetics

PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009758
Author(s):  
Sofie Claerhout ◽  
Paulien Verstraete ◽  
Liesbeth Warnez ◽  
Simon Vanpaemel ◽  
Maarten Larmuseau ◽  
...  
Keyword(s):  
Population Genetics ◽  
Y Chromosome ◽  
Tandem Repeats ◽  
Forensic Genetics ◽  
Genetic Research ◽  
Background Information ◽  
Nucleotide Polymorphisms ◽  
Wide Range ◽  
Male Specific ◽  
Paired End Sequencing

Male-specific Y-chromosome (chrY) polymorphisms are interesting components of the DNA for population genetics. While single nucleotide polymorphisms (Y-SNPs) indicate distant evolutionary ancestry, short tandem repeats (Y-STRs) are able to identify close familial kinships. Detailed chrY analysis provides thus both biogeographical background information as paternal lineage identification. The rapid advancement of high-throughput massive parallel sequencing (MPS) technology in the past decade has revolutionized genetic research. Using MPS, single-base information of both Y-SNPs as Y-STRs can be analyzed in a single assay typing multiple samples at once. In this study, we present the first extensive chrY-specific targeted resequencing panel, the ‘CSYseq’, which simultaneously identifies slow mutating Y-SNPs as evolution markers and rapid mutating Y-STRs as patrilineage markers. The panel was validated by paired-end sequencing of 130 males, distributed over 65 deep-rooted pedigrees covering 1,279 generations. The CSYseq successfully targets 15,611 Y-SNPs including 9,014 phylogenetic informative Y-SNPs to identify 1,443 human evolutionary Y-subhaplogroup lineages worldwide. In addition, the CSYseq properly targets 202 Y-STRs, including 81 slow, 68 moderate, 27 fast and 26 rapid mutating Y-STRs to individualize close paternal relatives. The targeted chrY markers cover a high average number of reads (Y-SNP = 717, Y-STR = 150), easy interpretation, powerful discrimination capacity and chrY specificity. The CSYseq is interesting for research on different time scales: to identify evolutionary ancestry, to find distant family and to discriminate closely related males. Therefore, this panel serves as a unique tool valuable for a wide range of genetic-genealogical applications in interdisciplinary research within evolutionary, population, molecular, medical and forensic genetics.

scholarly journals Chromosomal abnormalities and Y chromosome microdeletions in infertile men with azoospermia and oligozoospermia in Eastern China

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989671
Author(s):  
Jing Sha ◽  
Guiping Huang ◽  
Bei Zhang ◽  
Xia Wang ◽  
Zaochun Xu ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Assisted Reproduction ◽  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
Eastern China ◽  
Peripheral Blood Lymphocytes ◽  
Specific Sequence ◽  
Sequence Tagged Sites ◽  
Infertile Men ◽  
Y Chromosome Microdeletions

Objective The objective was to investigate the frequency and type of chromosomal abnormalities and Y chromosome microdeletions in infertile men with azoospermia and oligozoospermia to ensure appropriate genetic counseling before assisted reproduction in Eastern China. Methods A total of 201 infertile men (148 with azoospermia and 53 with oligozoospermia) were enrolled. Real-time PCR using six Y-specific sequence-tagged sites of the azoospermia factor (AZF) region was performed to screen for microdeletions. Karyotype analyses were performed on peripheral blood lymphocytes with standard G-banding. Results Out of 201 infertile patients, 22 (10.95%) had Y microdeletions [17/148 (11.49%) men with azoospermia and 5/53 (9.43%) men with oligozoospermia]. The most frequent microdeletions were in the AZFc region, followed by the AZFa+b + c, AZFb+c, AZFa, and AZFb regions. Chromosomal abnormalities were detected in 18.91% (38/201) of patients, 34 of which were sex chromosome abnormalities (16.92%) and 4 of which were autosomal abnormalities (1.99%). Chromosomal abnormalities were more prevalent in men with azoospermia (22.97%) than in those with oligozoospermia (7.55%). Conclusions We detected a high incidence of chromosomal abnormalities and Y chromosomal microdeletions in infertile Chinese men with azoospermia and oligozoospermia. These findings suggest the need for genetic testing before the use of assisted reproduction techniques.

scholarly journals Subdividing Y-chromosome haplogroup R1a1 reveals Norse Viking dispersal lineages in Britain

2020 ◽  
Author(s):  
Gurdeep Matharu Lall ◽  
Maarten H. D. Larmuseau ◽  
Jon H. Wetton ◽  
Chiara Batini ◽  
Pille Hallast ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Tandem Repeats ◽  
Viking Age ◽  
British Isles ◽  
Administrative Control ◽  
Y Chromosomes ◽  
Male Specific ◽  
Demographic Impact ◽  
Specific Contribution ◽  
Short Tandem

Abstract The influence of Viking-Age migrants to the British Isles is obvious in archaeological and place-names evidence, but their demographic impact has been unclear. Autosomal genetic analyses support Norse Viking contributions to parts of Britain, but show no signal corresponding to the Danelaw, the region under Scandinavian administrative control from the ninth to eleventh centuries. Y-chromosome haplogroup R1a1 has been considered as a possible marker for Viking migrations because of its high frequency in peninsular Scandinavia (Norway and Sweden). Here we select ten Y-SNPs to discriminate informatively among hg R1a1 sub-haplogroups in Europe, analyse these in 619 hg R1a1 Y chromosomes including 163 from the British Isles, and also type 23 short-tandem repeats (Y-STRs) to assess internal diversity. We find three specifically Western-European sub-haplogroups, two of which predominate in Norway and Sweden, and are also found in Britain; star-like features in the STR networks of these lineages indicate histories of expansion. We ask whether geographical distributions of hg R1a1 overall, and of the two sub-lineages in particular, correlate with regions of Scandinavian influence within Britain. Neither shows any frequency difference between regions that have higher (≥10%) or lower autosomal contributions from Norway and Sweden, but both are significantly overrepresented in the region corresponding to the Danelaw. These differences between autosomal and Y-chromosomal histories suggest either male-specific contribution, or the influence of patrilocality. Comparison of modern DNA with recently available ancient DNA data supports the interpretation that two sub-lineages of hg R1a1 spread with the Vikings from peninsular Scandinavia.

Evaluation of Y chromosome microdeletions and chromosomal anomalies in infertile men

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ozlem Oz
Keyword(s):  
Y Chromosome ◽  
Banding Technique ◽  
Chromosomal Anomalies ◽  
Specific Sequence ◽  
Sequence Tagged Sites ◽  
Infertile Men ◽  
Y Chromosome Microdeletions ◽  
Male Patients ◽  
Patient Selection Criteria ◽  
Methodological Aspects

Abstract Objectives Chromosome anomalies and Y chromosome microdeletions are one of the reasons that can be seen in infertile patients and affect fertility. In this study, it was aimed to determine the frequencies of chromosomal anomalies and Y chromosome microdeletions in primary infertile male patients. Methods We included 374 patients with primary infertility in this study. Cytogenetic analysis was performed with the GTG banding technique by using trypsin and Giemsa stain. Y microdeletion analysis was studied by multiplex polymerase chain reaction using 28 Y chromosome-specific sequence-tagged sites. Results Chromosomal irregularities were detected in 27 (7.22%) of infertile cases. It was observed that 7 (25.92%) of chromosomal irregularities detected in cases were in autosomal and 20 (%74.08) were in gonosomal chromosomes. The incidence of Y chromosome microdeletion was 1.07% (4/374) and the microdeletions were observed in AZFb, AZFc and AZFd regions. AZFc + AZFd deletion was detected in three patients (0.81%) and AZFb + AZFc + AZFd deletion in one patient (0.26%). Conclusions In conclusion, gonosomal chromosome irregularity was higher than autosomal chromosome irregularity in infertile men. The frequency of Y microdeletion has different rates according to some factors such as ethnic differences of patients, patient selection criteria, differences in the number of cases, and methodological aspects.

scholarly journals Divergence and Remarkable Diversity of the Y Chromosome in Guppies

2020 ◽  
Author(s):  
Pedro Almeida ◽  
Benjamin A Sandkam ◽  
Jake Morris ◽  
Iulia Darolti ◽  
Felix Breden ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Haplotype Diversity ◽  
Low Frequency ◽  
Color Variation ◽  
Recombination Suppression ◽  
Specific Sequence ◽  
Y Chromosome Evolution ◽  
Male Specific

Abstract The guppy sex chromosomes show an extraordinary diversity in divergence across populations and closely related species. In order to understand the dynamics of the guppy Y chromosome, we used linked-read sequencing to assess Y chromosome evolution and diversity across upstream and downstream population pairs that vary in predator and food abundance in three replicate watersheds. Based on our population-specific genome assemblies, we first confirmed and extended earlier reports of two strata on the guppy sex chromosomes. Stratum I shows significant accumulation of male-specific sequence, consistent with Y divergence, and predates the colonization of Trinidad. In contrast, Stratum II shows divergence from the X, but no Y-specific sequence, and this divergence is greater in three replicate upstream populations compared with their downstream pair. Despite longstanding assumptions that sex chromosome recombination suppression is achieved through inversions, we find no evidence of inversions associated with either Stratum I or Stratum II. Instead, we observe a remarkable diversity in Y chromosome haplotypes within each population, even in the ancestral Stratum I. This diversity is likely due to gradual mechanisms of recombination suppression, which, unlike an inversion, allow for the maintenance of multiple haplotypes. In addition, we show that this Y diversity is dominated by low-frequency haplotypes segregating in the population, suggesting a link between haplotype diversity and female preference for rare Y-linked color variation. Our results reveal the complex interplay between recombination suppression and Y chromosome divergence at the earliest stages of sex chromosome divergence.

Clinical, Hormonal, and Genetic Evaluation of Idiopathic Nonobstructive Azoospermia and Klinefelter Syndrome Patients

2017 ◽  
Vol 153 (4) ◽  
pp. 190-197 ◽  
Author(s):  
Shin Y. Kim ◽  
Bom Y. Lee ◽  
Ah R. Oh ◽  
So Y. Park ◽  
Hyo S. Lee ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Klinefelter Syndrome ◽  
Nonobstructive Azoospermia ◽  
Specific Sequence ◽  
Azoospermia Factor ◽  
Sequence Tagged Sites ◽  
Infertile Men ◽  
Y Chromosome Microdeletions ◽  
Genetic Abnormalities ◽  
Azf Region

To investigate the clinical, hormonal, and genetic factors in infertile men with idiopathic nonobstructive azoospermia (NOA) or azoospermic Klinefelter syndrome (KFS), a total of 556 and 96 patients, respectively, were included in this study. All patient samples were analyzed cytogenetically. Serum reproductive hormone levels were measured. Microdeletions in the azoospermia factor (AZF) region of the Y chromosome were detected by multiplex PCR using 16 specific sequence-tagged sites. FSH and LH levels in both NOA and KFS patients were significantly higher than the normal range, and the testosterone level in KFS patients was significantly lower. Ninety-two (95.8%) of the KFS patients showed non-mosaic 47,XXY karyotypes and 47,XXY,inv(9)(p11.1q13); the other KFS patients had mosaic karyotypes of 47,XXY/46,XY, 47,XXY/46,XX, and 47,XXY/48,XXXY/46,XX. Among the 556 idiopathic NOA patients with normal karyotypes, 67 (12.05%) had microdeletions in the AZF region of the Y chromosome. Microdeletions were most frequently detected in the AZFc region, followed by AZFa, AZFb, AZFbc, and partial AZFc deletions. However, Y chromosome microdeletions were not found in any of the azoospermic KFS patients. In view of the hormonal and genetic abnormalities in infertile men with idiopathic NOA and with azoospermic KFS, genetic testing for karyotype, Y chromosome microdeletions, and hormonal parameters is advocated.

scholarly journals Divergence and Remarkable Diversity of the Y Chromosome in Guppies

2020 ◽  
Author(s):  
Pedro Almeida ◽  
Benjamin A. Sandkam ◽  
Jake Morris ◽  
Iulia Darolti ◽  
Felix Breden ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Haplotype Diversity ◽  
Low Frequency ◽  
Recombination Suppression ◽  
Specific Sequence ◽  
Y Chromosome Evolution ◽  
Male Specific ◽  
Genome Assemblies

AbstractThe guppy sex chromosomes show an extraordinary diversity in divergence across populations and closely related species. In order to understand the dynamics of the guppy Y chromosome, we used linked-read sequencing to assess Y chromosome evolution and diversity across upstream and downstream population pairs that vary in predator and food abundance in three replicate watersheds. Based on our population-specific genome assemblies, we first confirmed and extended earlier reports of two strata on the guppy sex chromosomes. Stratum I shows significant accumulation of male-specific sequence, consistent with Y divergence, and predates the colonization of Trinidad. In contrast, Stratum II shows divergence from the X, but no Y-specific sequence, and this divergence is greater in three replicate upstream populations compared to their downstream pair. Despite longstanding assumptions that sex chromosome recombination suppression is achieved through inversions, we find no evidence of inversions associated with either Stratum I or Stratum II. Instead, we observe a remarkable diversity in Y chromosome haplotypes within each population, even in the ancestral Stratum I. This diversity is likely due to gradual mechanisms of recombination suppression, which, unlike an inversion, allow for the maintenance of multiple haplotypes. In addition, we show that this Y diversity is dominated by low-frequency haplotypes segregating in the population, suggesting a link between haplotype diversity and female-preference for rare Y-linked colour variation. Our results reveal the complex interplay between recombination suppression and Y chromosome divergence at the earliest stages of sex chromosome divergence.

scholarly journals Y chromosome is moving out of sex determination shadow

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Raheleh Heydari ◽  
Zohreh Jangravi ◽  
Samaneh Maleknia ◽  
Mehrshad Seresht-Ahmadi ◽  
Zahra Bahari ◽  
...  
Keyword(s):  
Sex Differences ◽  
Y Chromosome ◽  
Sex Hormones ◽  
Molecular Mechanisms ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Disease Mechanisms ◽  
Considerable Impact ◽  
Male Specific ◽  
Human Proteome Project

AbstractAlthough sex hormones play a key role in sex differences in susceptibility, severity, outcomes, and response to therapy of different diseases, sex chromosomes are also increasingly recognized as an important factor. Studies demonstrated that the Y chromosome is not a ‘genetic wasteland’ and can be a useful genetic marker for interpreting various male-specific physiological and pathophysiological characteristics. Y chromosome harbors male‑specific genes, which either solely or in cooperation with their X-counterpart, and independent or in conjunction with sex hormones have a considerable impact on basic physiology and disease mechanisms in most or all tissues development. Furthermore, loss of Y chromosome and/or aberrant expression of Y chromosome genes cause sex differences in disease mechanisms. With the launch of the human proteome project (HPP), the association of Y chromosome proteins with pathological conditions has been increasingly explored. In this review, the involvement of Y chromosome genes in male-specific diseases such as prostate cancer and the cases that are more prevalent in men, such as cardiovascular disease, neurological disease, and cancers, has been highlighted. Understanding the molecular mechanisms underlying Y chromosome-related diseases can have a significant impact on the prevention, diagnosis, and treatment of diseases.

scholarly journals Male linked genomic region determines sex in dioecious Amaranthus palmeri

2020 ◽  
Author(s):  
Cátia José Neves ◽  
Maor Matzrafi ◽  
Meik Thiele ◽  
Anne Lorant ◽  
Mohsen B Mesgaran ◽  
...  
Keyword(s):  
Sex Determination ◽  
Genetic Control ◽  
Y Chromosome ◽  
Weed Management ◽  
Draft Genome ◽  
Amaranthus Palmeri ◽  
Specific Sequence ◽  
Male And Female ◽  
Evolutionary State ◽  
Male Specific

Abstract Dioecy, the separation of reproductive organs on different individuals, has evolved repeatedly in different plant families. Several evolutionary paths to dioecy have been suggested, but the mechanisms behind sex determination is not well understood. The diploid dioecious Amaranthus palmeri represents a well suited model system to study sex determination in plants. Despite the agricultural importance of the species, the genetic control and evolutionary state of dioecy in A. palmeri is currently unknown. Early cytogenetic experiments did not identify heteromorphic chromosomes. Here, we used whole genome sequencing of male and female pools from two independent populations to elucidate the genetic control of dioecy in A. palmeri. Read alignment to a close monoecious relative and allele frequency comparisons between male and female pools did not reveal significant sex linked genes. Consequently, we employed an alignment free k-mer comparison which enabled us to identify a large number of male specific k-mers. We assembled male specific contigs comprising a total of almost 2 Mb sequence, proposing a XY sex determination system in the species. We were able to identify the potential Y chromosome in the A. palmeri draft genome sequence as 90 % of our male specific sequence aligned to a single scaffold. Based on our findings we suggest an intermediate evolutionary state of dioecy with a young Y chromosome in A. palmeri. Our findings give insight into the evolution of sex chromosomes in plants and may help to develop sustainable strategies for weed management.

Reaction-based Enumeration, Active Learning, and Free Energy Calculations to Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin Dependent Kinase 2 Inhibitors

2019 ◽  
Author(s):  
Kyle Konze ◽  
Pieter Bos ◽  
Markus Dahlgren ◽  
Karl Leswing ◽  
Ivan Tubert-Brohman ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Active Learning ◽  
Large Scale ◽  
Chemical Space ◽  
Population Based ◽  
Free Energy Calculations ◽  
Computational Technique ◽  
Cyclin Dependent Kinase ◽  
Energy Calculations

We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and cloud-based free energy calculations allows for large-scale potency predictions of compounds on a timescale that impacts drug discovery. The process is further accelerated by using a combination of population-based statistics and active learning techniques. Using this approach, we rapidly optimized R-groups and core hops for inhibitors of cyclin-dependent kinase 2. We explored greater than 300 thousand ideas and identified 35 ligands with diverse commercially available R-groups and a predicted IC<sub>50</sub> < 100 nM, and four unique cores with a predicted IC<sub>50</sub> < 100 nM. The rapid turnaround time, and scale of chemical exploration, suggests that this is a useful approach to accelerate the discovery of novel chemical matter in drug discovery campaigns.

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