Question

How can you explain the Polyphen predictions for genes PON1 and ATP5SL?

Answer 1

PON1 : disease : spinal dysraphism

SNP position: 192

Residue change : Q - R

Polyphen prediction : B

ATP5SL : disease: Alternative spicing.

SNP position: 159

Residue changes : S - C

Polyphen prediction: B

PolyPhen-2 (Polymorphism Phenotyping v2), available as software and via a Web server, predicts the possible impact of amino acid substitutions on the stability and function of human proteins using structural and comparative evolutionary considerations. It performs functional annotation of single-nucleotide polymorphisms (SNPs), maps coding SNPs to gene transcripts, extracts protein sequence annotations and structural attributes, and builds conservation profiles. It then estimates the probability of the missense mutation being damaging based on a combination of all these properties. PolyPhen-2 features include a high-quality multiple protein sequence alignment pipeline and a prediction method employing machine-learning classification. The software also integrates the UCSC Genome Browser's human genome annotations and MultiZ multiple alignments of vertebrate genomes with the human genome. PolyPhen-2 is capable of analyzing large volumes of data produced by next-generation.

Function of PON1 : The preferential association of PON1 with HDL is mediated in part by its signal peptide, by binding phospholipids directly, rather than binding apo AI. The retained signal peptide may allow transfer of the protein between phospholipid surfaces.

(NOTE: polyphen - 2 s an automatic tool for prediction of the possible impact of an amino acid substitution on the structure and function of a human protein. ... The prediction is based on a number of sequence, phylogenetic, and structural features characterizing the substitution.)

Thank You.