ABSTRACT
Our group tested three quality assessment functions in CASP8: a function which used only distance constraints derived from alignments (SAM-T08-MQAO), a function which added other single-model terms to the distance constraints (SAM-T08-MQAU), and a function which used both single-model and consensus terms (SAM-T08-MQAC). We analyzed the functions both for ranking models for a single target and for producing an accurate estimate of GDT_TS. Our functions were optimized for the ranking problem, so are perhaps more appropriate for metaserver applications than for providing trustworthiness estimates for single models. On the CASP8 test, the functions with more terms performed better. The MQAC consensus method was substantially better than either single-model function, and the MQAU function was substantially better than the MQAO function that used only constraints from alignments.
Subject(s)
Computational Biology/methods , Proteins/chemistry , Sequence Alignment/methods , Sequence Analysis, Protein/methods , Models, Molecular , Protein Conformation , SoftwareABSTRACT
Intellectual disability (ID) is a common developmental disability observed in 1 to 3% of the human population. A possible role for the Angiotensin II type 2 receptor (AGTR2) in brain function, affecting learning, memory, and behavior, has been suggested in humans and rodents. Mice lacking the Agtr2 gene (Agtr2(-/y)) showed significant impairment in their spatial memory and exhibited abnormal dendritic spine morphology. To identify Agtr2 influenced genes and pathways, we performed whole genome microarray analysis on RNA isolated from brains of Agtr2(-/y) and control male mice at embryonic day 15 (E15) and postnatal day one (P1). The gene expression profiles of the Agtr2(-/y) brain samples were significantly different when compared to profiles of the age-matched control brains. We identified 62 differently expressed genes (p< or =0.005) at E15 and in P1 brains of the Agtr2(-/y) mice. We verified the differential expression of several of these genes in brain samples using quantitative RT-PCR. Differentially expressed genes encode molecules involved in multiple cellular processes including microtubule functions associated with dendritic spine morphology. This study provides insight into Agtr2 influenced candidate genes and suggests that expression dysregulation of these genes may modulate Agtr2 actions in the brain that influences learning and memory.
Subject(s)
Biomarkers/metabolism , Brain/metabolism , Gene Expression Profiling , Gene Expression Regulation, Developmental , Receptor, Angiotensin, Type 2/physiology , Signal Transduction , Animals , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Oligonucleotide Array Sequence Analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
It was reported that positive selection has acted upon a gene involved in autosomal recessive primary microcephaly, Microcephalin (MCPH1/BRIT1), located at chromosome 8p23. We tested if the reported diagnostic single nucleotide polymorphism (SNP) (G37995C or c.940G > C) of a derived haplogroup of the MCPH1 gene had significantly different frequencies in mental retardation (MR) patients and in MR patients with microcephaly as compared to MR patients without microcephaly and controls in African-American and Caucasian populations in South Carolina, US. Our results suggest that there is little or no association between the MCPH1 c.940G allele and either microcephaly or MR. However, we found highly significant racial differences in the c.940G > C SNP allele frequencies between African-American and Caucasian populations.
Subject(s)
Intellectual Disability/genetics , Microcephaly/genetics , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide , Black or African American/genetics , Alleles , Base Sequence , Case-Control Studies , Cell Cycle Proteins , Chromosomes, Human, Pair 8/genetics , Cytoskeletal Proteins , DNA/blood , DNA/genetics , DNA Primers/genetics , Female , Gene Frequency , Humans , Intellectual Disability/complications , Male , Microcephaly/complications , Polymerase Chain Reaction , White People/geneticsABSTRACT
Growth curves are essential for determining whether growth parameters lie within normal ranges. In the case of fetal and neonatal autopsy, relevant data are scattered across many publications, and few sources examine a large enough sample to be considered definitive. To ameliorate these inadequacies, regressions were created incorporating data from multiple sources both to increase accuracy and to condense available data into a single standard. When measurements were not well studied, the best available published standards are given. These regressions provide a valuable tool for clinicians who need to understand the significance of measurements obtained during autopsy.
