Surprising genetic and pathological findings in a patient with giant bilateral periadrenal tumours: PEComas and mutations of PTCH1 in Gorlin-Goltz syndrome

Gorlin-Goltz syndrome (GGS) or nevoid basal cell carcinoma syndrome is a rare tumour-overgrowth syndrome associated with multiple developmental anomalies and a wide variety of tumours. Here, we describe a case of a man aged 23 years with GGS with bilateral giant tumours adjacent to both adrenals that raised the suspicion of malignancy on imaging. Histological analysis of both surgically resected tumours revealed perivascular epitheloid cell tumours (PEComas) that were independent of the adrenals. Exome sequencing of the patient’s blood sample revealed a novel germline heterozygous frameshift mutation in the PTCH1 gene. As a second hit, a somatic five nucleotide long deletion in the PTCH1 gene was demonstrated in the tumour DNA of both PEComas. To the best of our knowledge, this is the first report on PEComa in GGS, and this finding also raises the potential relevance of PTCH1 mutations and altered sonic hedgehog signalling in PEComa pathogenesis. The presence of the same somatic mutation in the bilateral tumours might indicate the possibility of a postzygotic somatic mutation that along with the germline mutation of the same gene could represent an intriguing genetic phenomenon (type 2 segmental mosaicism).

The phenomenon of reverse mutation in a patient with Wiskott–Aldrich syndrome

Primary immunodeficiencies (PIDS) are genetically caused heterogeneous diseases of the immune system. One of the genetic phenomenon affecting the phenotypic diversity of PIDS is a reverse somatic mosaicism (RM) observed in different groups of PIDS. The majority of RM cases are described in patients with Wiskott–Aldrich syndrome (WAS). Despite the fact that PM does not always lead to a mild form of the disease, the presence of this phenomenon can cause the delay of diagnosis and start of the appropriate treatment. This article presents the case of a patient with Wiskott–Aldrich syndrome with a reverse mutation in the WAS gene. Parents gave their consent to use information about the child in the article.

Rereading of the genetic origins of cancer: the puzzle of all eras

This is a scientific introduction to review the concept of cancer from a purely genetic perspective in which we try to link the development of tumors by the driving force of the evolution of living beings: the mutations. And to prove the assumption that cancer diversity has a parallel route instead of the whole development process of the cell. Calling for expanding the rolling concept of cancer and tumors definition in general. Which may contribute to altering the angle of our vision to this dangerous biological phenomenon. This call is based on the hypothesis that cancer is a genetic phenomenon that has arisen on the margins of the evolution process, that has continued since the beginning of creation. The pieces of evidence and indications that support this view were presented successively.

Rereading of the genetic origins of cancer: the puzzle of all eras

This is a scientific introduction to review the concept of cancer from a purely genetic perspective in which we try to link the development of tumors by the driving force of the evolution of living beings: the mutations. And to prove the assumption that cancer diversity has a parallel route instead of the whole development process of the cell. Calling for expanding the rolling concept of cancer and tumors definition in general. Which may contribute to altering the angle of our vision to this dangerous biological phenomenon. This call is based on the hypothesis that cancer is a genetic phenomenon that has arisen on the margins of the evolution process, that has continued since the beginning of creation. The pieces of evidence and indications that support this view were presented successively.

Inbreeding depression in crambe1

ABSTRACT Inbreeding depression in plants, caused by selfing or crossing among plants with a high degree of relatedness, is a genetic phenomenon that affects quantitative traits. This study aimed at verifying the occurrence of inbreeding depression in crambe progenies originated from selfing, in comparison with open pollination progenies. A randomized blocks design, with three replications, in a 32 x 2 factorial arrangement, with 32 crambe progenies and two reproduction systems (artificial selfing and open pollination), was used. Grain yield, 1,000-grain weight, plant height and final stand were evaluated. A significant interaction was observed between progenies and reproduction systems in all traits evaluated. A reduction in grain yield, 1,000-grain weight and plant height occurred in the majority of the selfing progenies, when compared to open pollination progenies. Inbreeding depression was observed in all traits, especially for grain yield. The heritability coefficients of selfed progenies were higher than the open pollinated ones, except for 1,000-grain weight.

Paternal Uniparental Disomy of Chromosome 14 with Hypospadias

Paternal uniparental disomy 14 (patUPD14) is a distinct, clinically recognizable syndrome. Using a clinical SNP microarray, we identified patUPD14 in a boy with a normal karyotype presenting cardiomyopathy and facial anomalies, a specific configuration of the thoracic ribs (‘coat hanger sign'), and hypospadias. Analyses of polymorphic microsatellites confirmed the diagnosis of patUPD14. We discuss the functions of the genes included in the rearrangement and their involvement in the pathogenesis of these disorders, especially hypospadias. ESR2 single nucleotide polymorphisms (rs944050; 2681-4A>G) have been associated with an increased risk of hypospadias in previous studies. The patient's ESR2 (rs944050) genotype is GG, whereas the parents both exhibit an AG genotype. This report sheds light on the genetic phenomenon in which the combination of a polymorphism and UPD can lead to new phenotypes, such as hypospadias.

Sporadic, global linkage disequilibrium between unlinked segregating sites

Demographic, genetic, or stochastic factors can lead to perfect linkage disequilibrium (LD) between alleles at two loci without respect to the extent of their physical distance, a phenomenon that Lawrence et al. (2005a) refer to as "genetic indistinguishability". This phenomenon can complicate genotype-phenotype association testing by hindering the ability to localize causal alleles, but has not been thoroughly explored from a theoretical perspective or using large, dense whole-genome polymorphism datasets. We derive a simple theoretical model of the prevalence of genetic indistinguishability between unlinked loci, and verify its accuracy via simulation. We show that sample size and minor allele frequency are the major determinants of the prevalence of perfect LD between unlinked loci but that demographic factors, such as deviations from random mating, can produce significant effects as well. Finally, we quantify this phenomenon in three model organisms and find thousands of pairs of moderate-frequency (>5%) genetically indistinguishable variants in relatively large datasets. These results clarify a previously underexplored population genetic phenomenon with important implications for association studies, and define conditions under which it is likely to manifest.

Research on Genetic Characteristics of Slab Bulge in Continuous Casting Process

Bulge deformation is an important factor that causes inner crack and declines the quality for slab. This has a significant genetic phenomenon in continuous casting process. In order to explain this feature, a two-dimensional FEM model for slab that includes viscoelastic and dynamic characteristic has been built. Positive creep and reverse creep were introduced to explain this mechanism. Roll pitch, shell characteristic, slab withdrawing speed and other process parameters that influence bulge’s genetic level are discussed. A nonlinear equation was suggested to describe the relationships between these factors and genetic level of bulge.

Exposure to Glycolytic Carbon Sources Reveals a Novel Layer of Regulation for the MalT Regulon

Bacteria adapt to changing environments by means of tightly coordinated regulatory circuits. The use of synthetic lethality, a genetic phenomenon in which the combination of two nonlethal mutations causes cell death, facilitates identification and study of such circuitry. In this study, we show that theE.coli ompR malTcondouble mutant exhibits a synthetic lethal phenotype that is environmentally conditional. MalTcon, the constitutively active form of the maltose system regulator MalT, causes elevated expression of the outer membrane porin LamB, which leads to death in the absence of the osmoregulator OmpR. However, the presence and metabolism of glycolytic carbon sources, such as sorbitol, promotes viability and unveils a novel layer of regulation within the complex circuitry that controls maltose transport and metabolism.

Combining ability of twelve maize populations

Genetic progress depends on germplasm quality and breeding methods. Twelve maize populations and their crosses were evaluated to estimate combining ability and potential to be included as source populations in breeding programs. Plant height, point of insertion of the first ear, number of ears per plant, number of grains per ear, root and stalk lodging and grain yield were studied in two locations in Brazil, during the 1997/98 season. Genotype sum of squares was divided into general (GCA) and specific (SCA) combining ability. Results indicated the existence of genetic divergence for all traits analyzed, where additive effects were predominant. The high heterosis levels observed, mainly in Xanxerê, suggested the environmental influence on the manifestation of this genetic phenomenon. Populations revealed potential to be used in breeding programs; however, those more intensively submitted to selection could provide larger genetic progress, showing the importance of population improvement for the increment of the heterosis in maize.