Cataloging Coding Sequence Variations in Human Genome Databases

نویسندگان

  • Hong-Hee Won
  • Hee-Jin Kim
  • Kyung-A Lee
  • Jong-Won Kim
چکیده

BACKGROUND With the recent growth of information on sequence variations in the human genome, predictions regarding the functional effects and relevance to disease phenotypes of coding sequence variations are becoming increasingly important. The aims of this study were to catalog protein-coding sequence variations (CVs) occurring in genetic variation databases and to use bioinformatic programs to analyze CVs. In addition, we aim to provide insight into the functionality of the reference databases. METHODOLOGY AND FINDINGS To catalog CVs on a genome-wide scale with regard to protein function and disease, we investigated three representative databases; the Human Gene Mutation Database (HGMD), the Single Nucleotide Polymorphisms database (dbSNP), and the Haplotype Map (HapMap). Using these three databases, we analyzed CVs at the protein function level with bioinformatic programs. We proposed a combinatorial approach using the Support Vector Machine (SVM) to increase the performance of the prediction programs. By cataloging the coding sequence variations using these databases, we found that 4.36% of CVs from HGMD are concurrently registered in dbSNP (8.11% of CVs from dbSNP are concurrent in HGMD). The pattern of substitutions and functional consequences predicted by three bioinformatic programs was significantly different among concurrent CVs, and CVs occurring solely in HGMD or in dbSNP. The experimental results showed that the proposed SVM combination noticeably outperformed the individual prediction programs. CONCLUSIONS This is the first study to compare human sequence variations in HGMD, dbSNP and HapMap at the genome-wide level. We found that a significant proportion of CVs in HGMD and dbSNP overlap, and we emphasize the need to use caution when interpreting the phenotypic relevance of these concurrent CVs. Combining bioinformatic programs can be helpful in predicting the functional consequences of CVs because it improved the performance of functional predictions.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Phylogenetic Analysis of Three Long Non-coding RNA Genes: AK082072, AK043754 and AK082467

Now, it is clear that protein is just one of the most functional products produced by the eukaryotic genome. Indeed, a major part of the human genome is transcribed to non-coding sequences than to the coding sequence of the protein. In this study, we selected three long non-coding RNAs namely AK082072, AK043754 and AK082467 which show brain expression and local region conservation among vertebr...

متن کامل

Identification of Human Cytomegalovirus pUL27 R233 point mutation using PCR-RFLP

Background and Aims: Human Cytomegalovirus (HCMV) is one of the life-threatening agents in immunosuppressed patients and congenitally infected neonates in the world. Mutations in UL27 were suggested to confer low- to high-grade Maribavir (MBV) resistance. As pUL27 R233S variation may involve in either MBV-resistance, we aimed to establish a method for identifying R233 coding sequence mutation...

متن کامل

Long non-coding RNAs and their significance in human diseases

Protein-coding genes account for only a small fraction of the human genome and most of the genomic sequences are transcriptionally silent, but recent observations indicate significant functional elements, including non-coding protein transcripts in the human genome. Long non-coding RNAs (lncRNAs) have been defined as transcripts of >200 nucleotides without protein-coding capacity that perform t...

متن کامل

Single Nucleotide Polymorphisms and Association Studies: A Few Critical Points

Uncovering DNA sequence variations that correlate with phenotypic changes, e.g., diseases, is the aim of sequence variation studies. Common types sequence variations are Single nucleotide polymorphism (SNP, pronounced snip).SNPs are the third-generation molecular marker. SNP represents a DNA sequence variant of a single base pair with the minor allele occurring in more than 1% of a given popula...

متن کامل

Production of Recombinant Adenovirus Containing Human Interlukin-4 Gene

Objective(s) Recombinant adenoviruses are currently used for a variety of purposes, including in vitro gene transfer, in vivo vaccination, and gene therapy. Ability to infect many cell types, high efficiency in gene transfer, entering both dividing and non dividing cells, and growing to high titers make this virus a good choice for using in various experiments. In the present experiment, a reco...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • PLoS ONE

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2008