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Молекулярные механизмы эволюции Поксвируса.

Считается, что поксивирусы развиваются относительно медленно, поскольку они являются двойными патогенами ДНК с корректирующими полимеразами. Однако оксивирусы имеют высокоприспособляемые геномы и могут претерпевать относительно быстрые генотипические и фенотипические изменения, о чем свидетельствует недавний рост передачи вируса обезьянопокс в организм человека. Достижения в технологии глубокой последовательности продемонстрировали постоянную вариацию нуклеотида у оксивирусных популяций, которая была недооценена. Появляется также понимание той роли, которую геномные архитектурные изменения игр

Совпадение в аннотации оригинала
Poxviruses are often thought to evolve relatively slowly because they are double-stranded DNA pathogens with proofreading polymerases. Howev … in shaping poxvirus evolution. These mechanisms include homologous and nonhomologous recombination, gene duplications, gene loss, and the acquisition of new genes through horizontal gene transfer. In this review, we discuss these evolutionary mechanisms and their potential roles for adaption to novel host species and modulating virulence.

Deeply conserved synteny resolves early events in vertebrate evolution.

Although it is widely believed that early vertebrate evolution was shaped by ancient whole-genome duplications, the number, timing and mechanism of these events remain elusive. Here, we infer the history of vertebrates through genomic comparisons with a new chromosome-scale sequence of the invertebrate chordate amphioxus. We show how the karyotypes of amphioxus and diverse vertebrates are derived from 17 ancestral chordate linkage groups (and 19 ancestral bilaterian groups) by fusion, rearrangement and duplication. We resolve two distinct ancient duplications based on patterns of chromosomal c

Characterization of the type I subgroup d IFN gene locus in large yellow croaker (larimichthys crocea) reveals a transposition-associated mechanism of type I IFN gene expansion in teleosts.

Type I interferons (IFNs) are key innate immune cytokines and have undergone extensive lineage-specific gene expansion during vertebrate evolution. Although IFN gene expansion has traditionally been attributed to local tandem duplication, whether alternative genomic mechanisms contribute to the diversification of type I IFN genes remains largely unexplored. Here, we identified an unusual expansion pattern of the type I subgroup d IFN gene (IFNd) in the large yellow croaker (Larimichthys crocea, Lc), revealing a potential transposition-associated mechanism underlying the duplication and relocat

Chromosomal translocation and segmental duplication in Cryptococcus neoformans.

Large chromosomal events such as translocations and segmental duplications enable rapid adaptation to new environments. Here we marshal genomic, genetic, meiotic mapping, and physical evidence to demonstrate that a chromosomal translocation and segmental duplication occurred during construction of a congenic strain pair in the fungal human pathogen Cryptococcus neoformans. Two chromosomes underwent telomere-telomere fusion, generating a dicentric chromosome that broke to produce a chromosomal translocation, forming two novel chromosomes sharing a large segmental duplication. The duplication sp

Convergent evolution through independent rearrangements in the primate amylase locus.

Structurally complex regions of the genome are increasingly recognized as engines of evolutionary convergence due to their propensity to generate recurrent gene duplications that give rise to similar gene expression patterns and traits across lineages. However the mutational mechanisms driving these duplications and the regulatory changes enabling novel expression patterns remain poorly understood. The primate amylase locus, marked by independent gene duplications, provides an ideal model to investigate these dynamics. Leveraging high-quality genome assemblies from 53 primates and multi-tissue…

Duplication of part of chromosome 17 is commonly associated with hereditary motor and sensory neuropathy type I (Charcot-Marie-Tooth disease type 1).

Hereditary motor and sensory neuropathy type I (HMSNI), also known as Charcot-Marie-Tooth disease type 1 (CMT1), has been shown to be genetically heterogeneous. A major gene maps to chromosome 17 (CMT1A). A set of loci, D17S122, D17S125, and D17S124, show tight linkage to the CMT1A locus, and a duplication of D17S122 has been detected in some families. We show that the locus D17S122 is duplicated in affected individuals from 7 informative families with HMSNI. The duplication was demonstrated either by differences in hybridization densities between two bands of a restriction fragment length pol

Heterozygous Beta Thalassemia with Segmental Duplication of chr16p13.3 Leading to Thalassemia Intermedia Phenotype: A Report of 2 Cases with Review of Literature.

Heterozygous β-thalassemia is typically asymptomatic, but when accompanied by α-globin gene multiplication, patients may exhibit clinical symptoms. We present two rare cases of heterozygous β-thalassemia where segmental duplications on chr16p13.3 led to increased α-globin gene copies, resulting in a thalassemia intermedia phenotype. One patient exhibited a novel de-novo duplication spanning 2.57 MB, while the other had a 173.8 KB duplication at the chr16p13.3 locus. These two cases are presented to underscore the significance of thorough and systematic evaluation in diagnosing rare forms of th

DISC1 duplication in two brothers with autism and mild mental retardation.

We describe the identification and delineation of an inherited 2.07 Mb microduplication in 1q42.2 in two brothers with autism and mild mental retardation. Since this duplication was not present in 1577 Belgian persons, we consider this as an extremely rare variant which has the potential to provide further insight into the genetics of autism. The duplication contains seven genes including the DISC1 gene, an interesting candidate gene that has been associated to schizophrenia, bipolar disorder, autism and Asperger syndrome. In this report we describe additional analyses undertaken to investigat

Genome-wide identification and characterization of bZIP transcription factors and their expression profile under abiotic stresses in Chinese pear (Pyrus bretschneideri).

BACKGROUND: In plants, basic leucine zipper transcription factors (TFs) play important roles in multiple biological processes such as anthesis, fruit growth & development and stress responses. However, systematic investigation and characterization of bZIP-TFs remain unclear in Chinese white pear. Chinese white pear is a fruit crop that has important nutritional and medicinal values. RESULTS: In this study, 62 bZIP genes were comprehensively identified from Chinese Pear, and 54 genes were distributed among 17 chromosomes. Frequent whole-genome duplication (WGD) and dispersed duplication (DSD)

Tandem inversion duplication within F8 Intron 1 associated with mild haemophilia A.

In approximately 90% of mild haemophilia A (HA) patients, a missense mutation can be identified using complete gene sequencing. In this study, multiplex ligation-dependent probe amplification analysis was performed as a second step in 10 French-speaking Belgian with mild HA presenting no detectable causal mutation by complete sequencing of the factor VIII (FVIII) (F8) gene's 26 exons and its 1.2 kb of contiguous promoter sequence. This gene dosage technique enabled the detection of exon 1 duplications of F8 in three apparently unrelated subjects. Using array-comparative genomic hybridization,

Identification of duplication downstream of BMP2 in a Chinese family with brachydactyly type A2 (BDA2).

Brachydactyly type A2 (BDA2, MIM 112600) is characterized by the deviation and shortening of the middle phalange of the index finger and the second toe. Using genome-wide linkage analysis in a Chinese BDA2 family, we mapped the maximum candidate interval of BDA2 to a ∼1.5 Mb region between D20S194 and D20S115 within chromosome 20p12.3 and found that the pairwise logarithm of the odds score was highest for marker D20S156 (Zmax = 6.09 at θ = 0). Based on functional and positional perspectives, the bone morphogenetic protein 2 (BMP2) gene was identified as the causal gene for BDA2 in this region,

De novo complex X chromosome rearrangement unmasking maternally inherited CSF2RA deletion in a girl with pulmonary alveolar proteinosis.

We report on a 3-year-old girl with a de novo complex X chromosome rearrangement associated with congenital pulmonary alveolar proteinosis (PAP) and short stature. Array comparative genome hybridization and FISH analyses contributed to characterize the complex rearrangement consisting of a 7.37 Mb terminal deletion of Xp22.33p22.2, a 17.3 Mb interstitial inverted duplication of Xp22.2p21.3, and a 10.14 Mb duplication of Xq27.3q28. PCR analysis of microsatellite markers supported a paternal origin of the X chromosome rearrangement. A pre-meiotic two-step mechanism may explain the occurrence of

Xq26.2-q26.3 microduplication in two brothers with intellectual disabilities: clinical and molecular characterization.

Partial duplications involving the long arm of the X chromosome are associated with mental retardation, short stature, microcephaly, hypopituitarism and a wide range of physical findings. We identified an inherited Xq26.2-Xq26.3 duplication in two brothers with severe mental retardation, hypotonia, growth delay, craniofacial disproportion and dental malocclusion. Chromosome analysis was normal and multiplex ligation-dependent probe amplification analysis detected duplication on Xq26. Further characterization by array comparative genomic hybridization and quantitative PCR helped to determine pr

[Identification of a novel pathogenic mutation in PDHA1 gene for pyruvate dehydrogenase complex deficiency].

OBJECTIVE: To study the molecular genetic mechanism and genetic diagnosis of pyruvate dehydrogenase complex deficiency (PHD), and to provide a basis for genetic counseling and prenatal genetic diagnosis of PHD. METHODS: Polymerase chain reaction (PCR) was performed to amplify the 11 exons and exon junction of the PDHA1 gene from a child who was diagnosed with PHD based on clinical characteristics and laboratory examination results. The PCR products were sequenced to determine the mutation. An analysis of amino acid conservation and prediction of protein secondary and tertiary structure were p

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function.

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is ubiquitously expressed in both the central nervous system and in the periphery. CHRNA7 is genetically linked to multiple disorders with cognitive deficits, including schizophrenia, bipolar disorder, ADHD, epilepsy, Alzheimer's disease, and Rett syndrome. The regulation of CHRNA7 is complex; more than a dozen mechanisms are known, one of which is a partial duplication of the parent gene. Exons 5-10 of CHRNA7 on chromosome 15 were duplicated and inserted 1.6 Mb upstream of CHRNA7, interrupting an earlier partial duplication

Golli-MBP copy number analysis by FISH, QMPSF and MAPH in 195 patients with hypomyelinating leukodystrophies.

The inherited disorders of CNS myelin formation represent a heterogeneous group of leukodystrophies. The proteolipoprotein (PLP1) gene has been implicated in two X-linked forms, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2, and the gap junction protein alpha12 (GJA12) gene in a recessive form of PMD. The myelin basic protein (MBP) gene, which encodes the second most abundant CNS myelin protein after PLP1, presents rearrangements in hypomyelinating murine mutants and is always included in the minimal region deleted in 18q- patients with an abnormal hypomyelination pattern on

The origin and diversification of a novel protein family in venomous snakes.

The genetic origins of novelty are a central interest of evolutionary biology. Most new proteins evolve from preexisting proteins but the evolutionary path from ancestral gene to novel protein is challenging to trace, and therefore the requirements for and order of coding sequence changes, expression changes, or gene duplication are not clear. Snake venoms are important novel traits that are comprised of toxins derived from several distinct protein families, but the genomic and evolutionary origins of most venom components are not understood. Here, we have traced the origin and diversification…

Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching.

Duplication at the Xq28 band including the MECP2 gene is one of the most common genomic rearrangements identified in neurodevelopmentally delayed males. Such duplications are non-recurrent and can be generated by a non-homologous end joining (NHEJ) mechanism. We investigated the potential mechanisms for MECP2 duplication and examined whether genomic architectural features may play a role in their origin using a custom designed 4-Mb tiling-path oligonucleotide array CGH assay. Each of the 30 patients analyzed showed a unique duplication varying in size from approximately 250 kb to approximately

Generation of induced pluripotent stem cell GZHMCi005-A from amniotic fluid-derived cells with duplication of chromosome 8p.

Cases in which the duplication of chromosome 8p (dup 8p) is observed are characterized by facial dysmorphism, agenesis/hypoplasia of the corpus callosum, heart defects and severe mental retardation. The frequency of dup 8p cases is higher compared to other chromosomes because of the Non-allelic homologous recombination (NAHR) between two segmental duplication regions (SDs) containing olfactory receptor gene clusters, REPD (repeat-distal) and REPP (repeat-proximal), located in chromosome 8p23.1. Here we generated a human iPSC line from a patient's amniotic fluid cells with a 18 Mb duplication i

Duplications and copy number variants of 8p23.1 are cytogenetically indistinguishable but distinct at the molecular level.

It has been proposed that duplications of 8p23.1 are either euchromatic variants of the 8p23.1 defensin domain with no phenotypic consequences or true duplications associated with developmental delay and heart defects. Here, we provide evidence for both alternatives in two new families. A duplication of most of band 8p23.1 (circa 5 Mb) was found in a girl of 8 years with pulmonary stenosis and mild language delay. BAC fluorescence in situ hybridisation (FISH) and multiplex amplifiable probe hybridisation (MAPH) showed that the two copies of the duplicated segment were sited, in an alternating