Three dimensional structure prediction of fatty acid binding site on human transmembrane receptor CD36

CD36 is an integral membrane protein which is thought to have a hairpin-like structure with alpha-helices at the C and N terminals projecting through the membrane as well as a larger extracellular loop. This receptor interacts with a number of ligands including oxidized low density lipoprotein and long chain fatty acids (LCFAs). It is also implicated in lipid metabolism and heart diseases. It is therefore important to determine the 3D structure of the CD36 site involved in lipid binding. In this study, we predict the 3D structure of the fatty acid (FA) binding site [127–279 aa] of the CD36 receptor based on homology modeling with X-ray structure of Human Muscle Fatty Acid Binding Protein (PDB code: 1HMT). Qualitative and quantitative analysis of the resulting model suggests that this model was reliable and stable, taking in consideration over 97.8% of the residues in the most favored regions as well as the significant overall quality factor. Protein analysis, which relied on the secondary structure prediction of the target sequence and the comparison of 1HMT and CD36 [127–279 aa] secondary structures, led to the determination of the amino acid sequence consensus. These results also led to the identification of the functional sites on CD36 and revealed the presence of residues which may play a major role during ligand-protein interactions

MatSAM: a Matlab implementation for Significance Analysis of Microarrays

Microarray experiments enable the simultaneous measure of expression levels of large amount of genes and have many applications. A widespread one is finding set of genes that are differentially expressed. Significance Analysis of Microarrays (SAM) helps to produce those sets using multiple testing techniques. There is unfortunately not yet a public tool enabling to do SAM using the Matlab platform. We here define MatSAM, a SAM implementation in Matlab, and show that it yields results of high confidence comparatively to those obtained by putative tools available in the R programming environment. MatSAM can be used in conjunction with Matlab Bioinformatics toolbox to perform further analysis.Availability: MatSAM is available as source code at  http://www.bioinfoindia.org/MatSA

Identification of single nucleotide variants in the Moroccan population by whole-genome sequencing

Background: Large-scale human sequencing projects have described around a hundred-million single nucleotide variants (SNVs). These studies have predominately involved individuals with European ancestry despite the fact that genetic diversity is expected to be highest in Africa where Homo sapiens evolved and has maintained a large population for the longest time. The African Genome Variation Project examined several African populations but these were all located south of the Sahara. Morocco is on the northwest coast of Africa and mostly lies north of the Sahara, which makes it very attractive for studying genetic diversity. The ancestry of present-day Moroccans is unknown and may be substantially different from Africans found South of the Sahara desert, Recent genomic data of Taforalt individuals in Eastern Morocco revealed 15,000-year-old modern humans and suggested that North African individuals may be genetically distinct from previously studied African populations. Results: We present SNVs discovered by whole genome sequencing (WGS) of three Moroccans. From a total of 5.9 million SNVs detected, over 200,000 were not identified by 1000G and were not in the extensive gnomAD database. We summarise the SNVs by genomic position, type of sequence gene context and effect on proteins encoded by the sequence. Analysis of the overall genomic information of the Moroccan individuals to individuals from 1000G supports the Moroccan population being distinct from both sub-Saharan African and European populations. Conclusions: We conclude that Moroccan samples are genetically distinct and lie in the middle of the previously observed cline between populations of European and African ancestry. WGS of Moroccan individuals can identify a large number of novel SNVs and aid in functional characterisation of the genome

Amplification of HER-2 Gene in Benign and Malignant Breast Lesions in a Sample of Iraqi Women

Background: Breast cancer is the most common cancer worldwide. From several markers of this malignancy, HER-2 is considered to have a particular importance because it associates with the treatment and prognosis of the disease. Objective: To investigate the amplification of HER-2 gene in benign and malignant lesions of breast in a sample of Iraqi women. Patients and Methods: A total of 24 excisional breast biopsies were obtained from women with breast lesions. Biopsies were preserved in 10% formalin and undergone paraffin embedding according to the standard protocol. Four µm thick sections were prepared and placed on positively charged slide and stained with fluorescent in situ hybridization. The stained slides were examined with fluorescence microscope to detect HER-2 gene amplification. Results: Fourteen women were found to have benign lesions, while 10 were with malignant lesions. All benign lesions revealed two copies of the gene while seven of  malignant cases showed positive results for HER-2 amplification (i.e more than 5 copies of the gene). Conclusion: These results support the idea that amplification of HER-2 could be considered as an indicator for tissue transformation into malignant lesion

The Ups and Downs of Mutation Frequencies during Aging Can Account for the Apert Syndrome Paternal Age Effect

Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2). The incidence of this disease increases with the age of the father (paternal age effect), and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

[Figure: see text]