Chromosomal mosaicism, the presence of two or more distinct cell lines, is prevalent throughout human pre- and post-implantation development and can lead to genetic abnormalities, miscarriages, stillbirths or live births. Due to the prevalence and significance of mosaicism in the human species, it is important to understand the origins, mechanisms and incidence of mosaicism throughout development.Literature searches were conducted utilizing Pubmed, with emphasis on human pre- and post-implantation mosaicism.Mosaicism persists in two separate forms: general and confined. General mosaicism is routine during human embryonic growth as detected by preimplantation genetic screening at either the cleavage or blastocyst stage, leading to mosaicism within both the placenta and fetus proper. Confined mosaicism has been reported in the brain, gonads and placenta, amongst other places. Mosaicism is derived from a variety of mechanisms including chromosome non-disjunction, anaphase lagging or endoreplication. Anaphase lagging has been implicated as the main process by which mosaicism arises in the preimplantation embryo. Furthermore, mosaicism can be caused by any one of numerous factors from paternal, maternal or exogenous factors such as culture media or possibly controlled ovarian hyperstimulation during in vitro fertilization (IVF). Mosaicism has been reported in as high as 70 and 90% of cleavage- and blastocyst-stage embryos derived from IVF, respectively.The clinical consequences of mosaicism depend on which chromosome is involved, and when and where an error occurs. Mitotic rescue of a meiotic error or a very early mitotic error will typically lead to general mosaicism while a mitotic error at a specific cell lineage point typically leads to confined mosaicism. The clinical consequences of mosaicism are dependent on numerous aspects, with the consequences being unique for each event.
The number of de novo genome sequence assemblies is increasing exponentially; however, relatively few contain one scaffold/contig per chromosome. Such assemblies are essential for studies of genotype-to-phenotype association, gross genomic evolution, and speciation. Inter-species differences can arise from chromosomal changes fixed during evolution, and we previously hypothesized that a higher fraction of elements under negative selection contributed to avian-specific phenotypes and avian genome organization stability. The objective of this study is to generate chromosome-level assemblies of three avian species (saker falcon, budgerigar, and ostrich) previously reported as karyotypically rearranged compared to most birds. We also test the hypothesis that the density of conserved non-coding elements is associated with the positions of evolutionary breakpoint regions.We used reference-assisted chromosome assembly, PCR, and lab-based molecular approaches, to generate chromosome-level assemblies of the three species. We mapped inter- and intrachromosomal changes from the avian ancestor, finding no interchromosomal rearrangements in the ostrich genome, despite it being previously described as chromosomally rearranged. We found that the average density of conserved non-coding elements in evolutionary breakpoint regions is significantly reduced. Fission evolutionary breakpoint regions have the lowest conserved non-coding element density, and intrachromomosomal evolutionary breakpoint regions have the highest.The tools used here can generate inexpensive, efficient chromosome-level assemblies, with > 80% assigned to chromosomes, which is comparable to genomes assembled using high-density physical or genetic mapping. Moreover, conserved non-coding elements are important factors in defining where rearrangements, especially interchromosomal, are fixed during evolution without deleterious effects.
Hyaluronic acid (HA)-binding is reported to predict the fertilising capacity of spermatozoa, while HA-bound sperm selection is reported to reduce the incidence of miscarriage. However, the clinical effectiveness of these techniques remains uncertain. This work investigated the prognostic value of sperm-HA binding (HAB) as a predictor of treatment outcomes, and whether HAB-sperm selection for Invitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) improves clinical outcomes or reduces miscarriage rates. A systematic review of the literature was carried out. A modified version of the Downs and Black Checklist was used to assess bias and study quality on eleven selected studies. No significant correlations were found between HAB score and fertilisation, clinical pregnancy, or live birth rates (low-quality evidence). Three studies reported a significant reduction in the incidence of miscarriage, including a Cochrane review (low-quality evidence). While the prognostic value of HAB scores is currently undetermined, there is evidence that HAB-sperm selection prior to insemination reduces the incidence of miscarriage following ART. Moreover, there are no reports of detrimental effects of HAB-sperm selection on treatment outcomes when compared with conventional IVF or ICSI. Therefore, it is unclear why it is assigned as a treatment “add-on” with a red light by the HFEA, and why its routine use is not recommended.
Determining the nuclear 'addresses' of chromosome territories is a well-documented means of assaying for nuclear organisation in many cell types and species. Data in avian species are however limited at best, despite the pivotal role played by birds (particularly chickens) in agriculture, and as model organisms in developmental biology. That is, studies have hitherto focussed mostly on mammals (especially humans) and have demonstrated the importance of chromosome territory positioning in embryology, disease and evolution. Thus a detailed study of nuclear organisation in many species, many cell types and many developmental stages in birds is warranted, however, before this is achieved, 'baseline' needs to be established to determine precisely the relative locations of chromosome territories in at least 1 cell type of at least 1 bird. With this in mind we hybridised FISH probes from chicken chromosomes 1-28 to embryonic fibroblast nuclei, determining nuclear addresses using a newly developed plug-in to the image analysis package ImageJ. In our experience, evenly spaced representative BAC clones yielded more consistent results than hybridisation of chromosome paints. Results suggested that chromosome territory distribution best fitted a chromosome size-based (rather than gene density-based) pattern. Identical BAC clones were then hybridised to turkey and duck in a comparative genomic strategy. Observations were consistent with those seen in chicken (although, less well-defined in duck), providing preliminary evidence of conservation throughout evolution.
There has been a recent explosion in avian genomics. In December 2014 the Beijing Genomics Institute in collaboration with a number of labs worldwide (including Kent) released 48 new de-novo avian genome sequences in a special edition of Science. This has led to a complete re-evaluation of the phylogenetic tree of birds and presents the opportunity to study avian comparative genomics in far more detail than before. Most of these genome sequences however exist only as “scaffolds” i.e. the depth of sequence and length of read produces contiguous fragments of sub-chromosomal size. This impedes insight into overall genome structure, which is particularly challenging, as one of the most interesting biological features of birds is the peculiarity of their karyotype. This project is an on-going effort to map scaffold assemblies to avian chromosomes using a combination of bioinformatics and Fluorescent in situ Hybridization (FISH). This has traditionally been a very time-consuming and costly procedure, however a combination of bioinformatic approaches coupled with novel hardware innovation has deconstructed the FISH protocol and re-invented it as a high throughput, cheaper procedure. Initial work has helped to reconstruct Pigeon and Peregrine Falcon genomes and will ultimately provide insight into various unanswered questions pertaining to avian gross genome rearrangement. These include why the unique overall genomic structure of birds is so evolutionarily conserved, why intra and inter-chromosomal rearrangements happen (e.g. in response to the development of traits such as vocal learning) and what the karyotypes of extinct species such as dinosaurs may have looked like.
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