COMPARISON OF EUPLOID DONOR EGG BLASTOCYST EXPANSION WITH SUBGROUPS OF SINGLE CHROMOSOME, MULTIPLE CHROMOSOME, AND SEGMENTAL ANEUPLOIDY CALLS USING AN AI PLATFORM

Abstract Background Microarray-based and next generation sequencing (NGS) technologies have revealed that segmental aneuploidy is frequently present in human oocytes, cleavage-stage embryos and blastocysts. However, very little research has analyzed the type, size, chromosomal distribution and topography of the chromosomal segments at the different stages of development. Methods This is a retrospective study of 822 PGT-A (preimplantation genetic test for aneuploidies) performed on trophectoderm samples from 3565 blastocysts biopsied between January 2016 and April 2017. The cycles in question had been initiated for varying clinical indications. Samples were analyzed by next generation sequencing-based technology. Segmental aneuploidies were evaluated when fragment size was > 5 Mb. Blastocysts presenting a single segmental aneuploidy (SSA), without any additional whole-chromosome gain/loss, were statistically analyzed for incidence, type, size and chromosomal emplacement. Segment sizes relative to the whole chromosome or arm (chromosome- and arm-ratios) were also studied. Results 8.4% (299/3565) of blastocysts exhibited segmental aneuploidy for one or more chromosomes, some of which were associated with whole-chromosome aneuploidy while others were not. Nearly half of them (4.5%: 159/3565 of blastocysts) exhibited pure-SSA, meaning that a single chromosome was affected by a SSA. Segments were more frequent in medium-sized metacentric or submetacentric chromosomes and particularly in q-chrmosome arms, variables that were related to trophectoderm quality. SSA size was related to a greater extent to chromosome number and the arm affected than it was to SSA type. In absolute values (Mb), SSA size was larger in large chromosomes. However, the SSA:chromosome ratio was constant across all chromosomes and never exceeded 50% of the chromosome. Conclusions SSA frequency is chromosome- and topographically dependent, and its incidence is not related to clinical or embryological factors, but rather to trophectoderm quality. SSA might be originated by chromosome instability in response to chromothripsis, bias introduced by the biopsy and/or iatrogenic effects. Trial registration Retrospectively registered.

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Accurate detection of small segmental aneuploidy using next generation screening in preimplantation genetic diagnose and screening (PGD/PGS)

10.26226/morressier.5912d9eed462b80292386515 ◽

2017 ◽

Author(s):

zhou shuang

Keyword(s):

Next Generation ◽

Accurate Detection ◽

Segmental Aneuploidy

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Euploidy rates in donor egg cycles are significantly influenced by the number of accumulated ovarian stimulations.

10.26226/morressier.5af300b0738ab10027aa96a9 ◽

2018 ◽

Author(s):

Inmaculada Jurado Garcia ◽

Jonas Sarasa ◽

Cristina Real Llinares ◽

Blanca Rodriguez-Estrada ◽

Ismael Vilella Amorós ◽

...

Keyword(s):

Donor Egg ◽

Euploidy Rates

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Analysis of Inter-Chromosomal Distribution of Disease-Related Genes in Human Genome

Current Protein and Peptide Science ◽

10.2174/1389203721666200426233158 ◽

2020 ◽

Vol 21 (11) ◽

pp. 1068-1077

Author(s):

Xiaochao Sun ◽

Bin Yang ◽

Qunye Zhang

Keyword(s):

Spatial Distribution ◽

Model Organisms ◽

Nucleotide Polymorphisms ◽

Chromosomal Distribution ◽

Single Nucleotide ◽

Protein Coding ◽

Single Chromosome ◽

Deletion Mutations ◽

Protein Coding Genes ◽

Disease Related Genes

: Many studies have shown that the spatial distribution of genes within a single chromosome exhibits distinct patterns. However, little is known about the characteristics of inter-chromosomal distribution of genes (including protein-coding genes, processed transcripts and pseudogenes) in different genomes. In this study, we explored these issues using the available genomic data of both human and model organisms. Moreover, we also analyzed the distribution pattern of protein-coding genes that have been associated with 14 common diseases and the insert/deletion mutations and single nucleotide polymorphisms detected by whole genome sequencing in an acute promyelocyte leukemia patient. We obtained the following novel findings. Firstly, inter-chromosomal distribution of genes displays a nonstochastic pattern and the gene densities in different chromosomes are heterogeneous. This kind of heterogeneity is observed in genomes of both lower and higher species. Secondly, protein-coding genes involved in certain biological processes tend to be enriched in one or a few chromosomes. Our findings have added new insights into our understanding of the spatial distribution of genome and disease- related genes across chromosomes. These results could be useful in improving the efficiency of disease-associated gene screening studies by targeting specific chromosomes.

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Dating the primigenial C4-CYP21 duplication in primates.

Genetics ◽

10.1093/genetics/134.1.331 ◽

1993 ◽

Vol 134 (1) ◽

pp. 331-339 ◽

Cited By ~ 1

Author(s):

Y Horiuchi ◽

H Kawaguchi ◽

F Figueroa ◽

C O'hUigin ◽

J Klein

Keyword(s):

World Monkey ◽

Orthologous Genes ◽

Pigtail Macaque ◽

Single Chromosome ◽

Old World ◽

Histocompatibility Complex ◽

Cyp21 Gene ◽

Multiple Copies ◽

Fourth Component ◽

Flanking Regions

Abstract C4 and CYP21 are two adjacent, but functionally unrelated genes residing in the middle of the mammalian major histocompatibility complex (Mhc). The C4 gene codes for the fourth component of the complement cascade, whereas the CYP21 gene specifies an enzyme (cytochrome P450c21) of the glucocorticoid and mineralocorticoid pathways. The genes occur frequently in multiple copies on a single chromosome arranged in the order C4 ... CYP21 ... C4 ... CYP21. The unit of duplication (a module) is the C4-CYP21 gene pair. We sequenced the flanking regions of the C4-CYP21 modules and the intermodular regions of the chimpanzee, gorilla, and orangutan, as well as the intermodular region of an Old World monkey, the pigtail macaque. By aligning the sequences, we could identify the duplication breakpoints in these species. The breakpoint turned out to be at exactly the same position as that found previously in humans. The sequences flanking paralogous genes in the same species were found to be more similar to one another than sequences flanking orthologous genes in different species. We interpret these results as indicating that the original (primigenial) duplication occurred before the separation of apes from Old World monkeys more than 23 million years ago. The nature of the sequence at the breakpoint suggests that the duplication occurred by nonhomologous recombination. Since then, the C4-CYP21 haplotypes have been expanding and contracting by homologous crossing over which has homogenized the sequences in each species.(ABSTRACT TRUNCATED AT 250 WORDS)

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A Haplolethal Locus Uncovered by Deletions in the Mouse t Complex

Genetics ◽

10.1093/genetics/160.2.675 ◽

2002 ◽

Vol 160 (2) ◽

pp. 675-682

Author(s):

Victoria L Browning ◽

Rebecca A Bergstrom ◽

Sandra Daigle ◽

John C Schimenti

Keyword(s):

Gene Dosage ◽

Es Cells ◽

Embryonic Stem ◽

Chromosome 17 ◽

Mammalian Development ◽

T Complex ◽

Segmental Aneuploidy ◽

Systematic Exploration ◽

Radiation Induced ◽

Altered Gene

Abstract Proper levels of gene expression are important for normal mammalian development. Typically, altered gene dosage caused by karyotypic abnormalities results in embryonic lethality or birth defects. Segmental aneuploidy can be compatible with life but often results in contiguous gene syndromes. The ability to manipulate the mouse genome allows the systematic exploration of regions that are affected by alterations in gene dosage. To explore the effects of segmental haploidy in the mouse t complex on chromosome 17, radiation-induced deletion complexes centered at the Sod2 and D17Leh94 loci were generated in embryonic stem (ES) cells. A small interval was identified that, when hemizygous, caused specific embryonic lethal phenotypes (exencephaly and edema) in most fetuses. The penetrance of these phenotypes was background dependent. Additionally, evidence for parent-of-origin effects was observed. This genetic approach should be useful for identifying genes that are imprinted or whose dosage is critical for normal embryonic development.

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A DNA Sequence Based Polymer Model for Chromatin Folding

International Journal of Molecular Sciences ◽

10.3390/ijms22031328 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1328

Author(s):

Rui Zhou ◽

Yi Qin Gao

Keyword(s):

Dna Sequence ◽

Cpg Island ◽

Coarse Grained ◽

Chromosome Territories ◽

Base Pairs ◽

Single Chromosome ◽

Power Law Decay ◽

Multiple Length Scales ◽

Spatial Domains ◽

Chromatin Folding

The recent development of sequencing technology and imaging methods has provided an unprecedented understanding of the inter-phase chromatin folding in mammalian nuclei. It was found that chromatin folds into topological-associated domains (TADs) of hundreds of kilo base pairs (kbps), and is further divided into spatially segregated compartments (A and B). The compartment B tends to be located near to the periphery or the nuclear center and interacts with other domains of compartments B, while compartment A tends to be located between compartment B and interacts inside the domains. These spatial domains are found to highly correlate with the mosaic CpG island (CGI) density. High CGI density corresponds to compartments A and small TADs, and vice versa. The variation of contact probability as a function of sequential distance roughly follows a power-law decay. Different chromosomes tend to segregate to occupy different chromosome territories. A model that can integrate these properties at multiple length scales and match many aspects is highly desired. Here, we report a DNA-sequence based coarse-grained block copolymer model that considers different interactions between blocks of different CGI density, interactions of TAD formation, as well as interactions between chromatin and the nuclear envelope. This model captures the various single-chromosome properties and partially reproduces the formation of chromosome territories.

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Frequent tRNA gene translocation towards the boundaries with control regions contributes to the highly dynamic mitochondrial genome organization of the parasitic lice of mammals

BMC Genomics ◽

10.1186/s12864-021-07859-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wen-Ge Dong ◽

Yalun Dong ◽

Xian-Guo Guo ◽

Renfu Shao

Keyword(s):

Mitochondrial Genome ◽

Control Region ◽

Genome Organization ◽

Trna Gene ◽

Trna Genes ◽

Single Chromosome ◽

Gene Translocation ◽

Sucking Lice ◽

Different Types ◽

Mt Genome

Abstract Background The typical single-chromosome mitochondrial (mt) genome of animals has fragmented into multiple minichromosomes in the lineage Mitodivisia, which contains most of the parasitic lice of eutherian mammals. These parasitic lice differ from each other even among congeneric species in mt karyotype, i.e. the number of minichromosomes, and the gene content and gene order in each minichromosome, which is in stark contrast to the extremely conserved single-chromosome mt genomes across most animal lineages. How fragmented mt genomes evolved is still poorly understood. We use Polyplax sucking lice as a model to investigate how tRNA gene translocation shapes the dynamic mt karyotypes. Results We sequenced the full mt genome of the Asian grey shrew louse, Polyplax reclinata. We then inferred the ancestral mt karyotype for Polyplax lice and compared it with the mt karyotypes of the three Polyplax species sequenced to date. We found that tRNA genes were entirely responsible for mt karyotype variation among these three species of Polyplax lice. Furthermore, tRNA gene translocation observed in Polyplax lice was only between different types of minichromosomes and towards the boundaries with the control region. A similar pattern of tRNA gene translocation can also been seen in other sucking lice with fragmented mt genomes. Conclusions We conclude that inter-minichromosomal tRNA gene translocation orientated towards the boundaries with the control region is a major contributing factor to the highly dynamic mitochondrial genome organization in the parasitic lice of mammals.

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A Novel Ty1-Mediated Fragmentation Method for Native and Artificial Yeast Chromosomes Reveals That the Mouse Steel Gene is a Hotspot for Ty1 Integration

Genetics ◽

10.1093/genetics/143.2.673 ◽

1996 ◽

Vol 143 (2) ◽

pp. 673-683

Author(s):

Jacob Z Dalgaard ◽

Mukti Banerjee ◽

M Joan Curcio

Keyword(s):

Transcription Unit ◽

Yeast Genome ◽

Physical Analysis ◽

Single Chromosome ◽

Artificial Chromosomes ◽

Unique Site ◽

High Fraction ◽

A Site ◽

Yeast Artificial Chromosomes ◽

Random Insertion

Abstract We have developed a powerful new tool for the physical analysis of genomes called Ty1-mediated chromosomal fragmentation and have used the method to map 24 retrotransposon insertions into two different mousederived yeast artificial chromosomes (YACs). Expression of a plasmid-encoded GAL1:Ty1 fusion element marked with the retrotransposition indicator gene, ade2AI, resulted in a high fraction of cells that sustained a single Ty1 insertion marked with ADE2. Strains in which Ty1ADE2 inserted into aYAC were identified by cosegregation of the ADE2 gene with the URA3-marked YAC. Ty1ADE2 elements also carried a site for the endonuclease I-DmoI, which we demonstrate is not present anywhere in the yeast genome. Consequently, I-DmoI cleaved a single chromosome or YAC at the unique site of Ty1ADE2 insertion, allowing rapid mapping of integration events. Our analyses showed that the frequency of Ty1ADE2 integration into YACs is equivalent to or higher than that expected based on random insertion. Remarkably, the 50-kb transcription unit of the mouse Steel locus was shown to be a highly significant hotspot for Ty1 integration. The accessibility of mammalian transcription units to Ty1 insertion stands in contrast to that of yeast transcription units.

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A Demonstration of a 1:1 Correspondence Between Chiasma Frequency and Recombination Using a Lolium perenne/Festuca pratensis Substitution

Genetics ◽

10.1093/genetics/161.1.307 ◽

2002 ◽

Vol 161 (1) ◽

pp. 307-314 ◽

Cited By ~ 7

Author(s):

J King ◽

L A Roberts ◽

M J Kearsey ◽

H M Thomas ◽

R N Jones ◽

...

Keyword(s):

Lolium Perenne ◽

Chiasma Frequency ◽

Chiasma Formation ◽

Grass Species ◽

Festuca Pratensis ◽

Single Chromosome ◽

Length Polymorphisms ◽

Amplified Fragment Length Polymorphisms ◽

Frequency Counts

Abstract A single chromosome of the grass species Festuca pratensis has been introgressed into Lolium perenne to produce a diploid monosomic substitution line (2n = 2x = 14). The chromatin of F. pratensis and L. perenne can be distinguished by genomic in situ hybridization (GISH), and it is therefore possible to visualize the substituted F. pratensis chromosome in the L. perenne background and to study chiasma formation in a single marked bivalent. Recombination occurs freely in the F. pratensis/L. perenne bivalent, and chiasma frequency counts give a predicted map length for this bivalent of 76 cM. The substituted F. pratensis chromosome was also mapped with 104 EcoRI/Tru91 and HindIII/Tru91 amplified fragment length polymorphisms (AFLPs), generating a marker map of 81 cM. This map length is almost identical to the map length of 76 cM predicted from the chiasma frequency data. The work demonstrates a 1:1 correspondence between chiasma frequency and recombination and, in addition, the absence of chromatid interference across the Festuca and Lolium centromeres.

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