Energy-harnessing problem solving of primordial life: Modeling the emergence of catalytic host-nested parasite life cycles.

All life forms on earth ultimately descended from a primordial population dubbed the last universal common ancestor or LUCA via Darwinian evolution. Extant living systems share two salient functional features, a metabolism extracting and transforming energy required for survival, and an evolvable, informational polymer-the genome-conferring heredity. Genome replication invariably generates essential and ubiquitous genetic parasites.

Cell-free DNA testing of an extended range of chromosomal anomalies: clinical experience with 6,388 consecutive cases.

Purpose: Cell-free DNA (cfDNA) testing for fetal aneuploidies was broadly implemented for common trisomies and sex-chromosome anomalies (SCAs). However, such an approach identifies only 75 to 85% of clinically relevant aneuploidies.

Methods: We present a consecutive series of 6,388 cases, thus uncovering a broader array of aneuploidies, including the rare autosomal trisomies (RATs) and the maternally inherited deletion and duplication copy-number variations (CNVs), with complete and stratified follow-up by amniocentesis.

Clinical, functional and genetic analysis of twenty-four patients with chronic granulomatous disease - identification of eight novel mutations in CYBB and NCF2 genes.

Chronic granulomatous disease is an inherited disorder in which phagocytes lack a functional NADPH oxidase and cannot produce superoxide anions. The most common form is caused by mutations in CYBB encoding gp91phox. We investigated 24 CGD patients and their families.

Neuropsychological impairments and the impact of dystrophin mutations on general cognitive functioning of patients with Duchenne muscular dystrophy.

Mutations in the dystrophin gene have long been recognised as a cause of mental retardation. However, for reasons that are unclear, some boys with dystrophin mutations do not show general cognitive deficits. To investigate the relationship between dystrophin mutations and cognition, the general intellectual abilities of a group of 25 boys with genetically confirmed Duchenne muscular dystrophy were evaluated.

A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes.

Context: Both biallelic and monoallelic mutations in PROK2 or PROKR2 have been found in Kallmann syndrome (KS).

Objective: The objective of the study was to compare the phenotypes of KS patients harboring monoallelic and biallelic mutations in these genes.

Design And Patients: We studied clinical and endocrine features that reflect the functioning of the pituitary-gonadal axis, and the nonreproductive phenotype, in 55 adult KS patients (42 men and 13 women), of whom 41 had monoallelic mutations and 14 biallelic mutations in PROK2 or PROKR2.

Unilateral focal polymicrogyria in a patient with classical Aarskog-Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1.

Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is an X-linked disorder characterized by craniofacial, skeletal, and urogenital malformations and short stature. Mutations in the only known causative gene FGD1 are found in about one-fifth of the cases with the clinical diagnosis of AAS. FGD1 is a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42 via its RhoGEF domain.

A de novo 1.1-1.6 Mb subtelomeric deletion of chromosome 20q13.33 in a patient with learning difficulties but without obvious dysmorphic features.

We report on a de novo submicroscopic deletion of 20q13.33 identified by subtelomeric fluorescence in situ hybridization (FISH) in a 4-year-old girl with learning difficulties, hyperlaxity and strabismus, but without obvious dysmorphic features. Further investigations by array-based comparative genomic hybridization (array-CGH) and FISH analysis allowed us to delineate the smallest reported subterminal deletion of chromosome 20q, spanning a 1.

Gene duplication: a drive for phenotypic diversity and cause of human disease.

Gene duplication is one of the key factors driving genetic innovation, i.e., producing novel genetic variants.

Transcriptional activation by bidirectional RNA polymerase II elongation over a silent promoter.

Transcriptional interference denotes negative cis effects between promoters. Here, we show that promoters can also interact positively. Bidirectional RNA polymerase II (Pol II) elongation over the silent human endogenous retrovirus (HERV)-K 18 promoter (representative of 2.

[Rapid prenatal diagnosis of chromosome abnormalities: from FISH to QF-PCR].

Prenatal diagnosis for pregnancies at increased risk for chromosome abnormalities is routinely undertaken by karyotype analysis. While karyotype analysis remains the standard method to detect structural and copy number changes of chromosomes, it requires prolonged cell culture resulting in average reporting times of about two weeks. To relieve parental anxiety, and improve the quality and plasticity of pregnancy management, rapid methods, such as FISH and QF-PCR have recently been developed.

Negative thymocyte selection to HERV-K18 superantigens in humans.

An experimental system to explore central tolerance in humans is unavailable. However, the human endogenous retrovirus K-18 (HERV-K18) region on chromosome 1 provides an excellent model: HERV-K18 encodes a superantigen (SAg) stimulating Vbeta7CD4 T cells that is implicated in type 1 diabetes and Epstein-Barr virus persistence. In this study, we have addressed thymic HERV-K18 SAg expression, the capacity of SAg to induce negative selection, and the consequences of this for peripheral tolerance compared with SAg reactivity.

Novel procedures for high-throughput analysis of a frequent insertion-deletion polymorphism in the human T-cell receptor beta locus.

The human T-cell receptor beta locus ( TRB) contains two frequent insertion-deletion polymorphisms. In one, the insertion comprises two functional variable beta genes, TRBV6-2/TRBV6-3 and TRBV4-3, and the pseudogene TRBV3-2. Deletion of these TRBV genes may confer resistance and/or susceptibility to autoimmunity, analogously to findings in rodent models.

Association of human endogenous retrovirus K-18 polymorphisms with type 1 diabetes.

Several lines of evidence suggest the involvement of the human endogenous retrovirus (HERV)-K18 in the etiology of type 1 diabetes. HERV-K18 encodes for a T-cell superantigen (SAg). T-cells with T-cell receptor Vbeta7 chains reactive to the SAg and HERV-K18 mRNA were enriched in the tissues at the onset of the disease.

Potential mechanisms of interferon-alpha induced autoimmunity.

The type I interferons (IFN) are cytokines encoded by a multigene family comprising 13 closely related IFN-A genes, and a single IFN-B gene. These factors are rapidly induced upon viral infection, and have pleiotropic effects. Historically, the induction of a cell-autonomous state of antiviral resistance, the inhibition of cell growth, and the regulation of apoptosis were appreciated first.