Introduction to Bioinformatics and Diagnostics

Introduction to Bioinformatics

• Bioinformatics is the application of statistics and computer science to molecular biology
• It involves organizing biological data and extracting relevant information.

Detecting Genetic Diseases

• Fetal testing identifies chromosome abnormalities and defective genes
  • Amniocentesis (16 weeks, karyotype)
  • Chorionic villus sampling (8-10 weeks, karyotype)
• Testing for chromosome abnormalities and defective genes also involves:
  • Fluorescence in situ hybridization (FISH)
    • Uses fluorescent probes specific to chromosomes or genes
  • Spectral karyotyping

Molecular Diagnostics

• Molecular diagnostics uses DNA, RNA, and proteins to detect, diagnose, subclassify, predict the course of disease, and monitor responses to treatment.
• Advantages include improved sensitivity, high specificity, lower cost, and faster analysis time.

Microarray Technology

• Microarrays are chips with thousands of single-stranded DNA molecules.
• DNA from a patient is isolated, labeled, hybridized to the microarray
• A laser scanner measures the fluorescence intensity to identify SNPs or genes the patient's DNA binds to.
• Used to compare gene expression levels between different tissues and is applied to cancer research.

Allele-Specific Oligonucleotide (ASO) Dot Blot

• A method used to detect SNPs and disease markers.
• PCR amplified DNA is blotted onto a membrane, unbound probes are washed off, and bound probes are detected by radioactive or colorimetric assays.
• Applied for detection of sickle cell anemia

Reverse Dot Blot

• Instead of binding DNA to the membrane, an array of ASOs (allele-specific oligonucleotides) is bound to a membrane and hybridized to labeled target DNA.
• Used to analyze patient DNA for genetic markers/mutations.

Single Nucleotide Polymorphisms (SNPs)

• SNPs are one of the most common forms of genetic variation.
• Roughly one SNP occurs every 1,000-3,000 base pairs (bp) in human DNA.
• Most SNPs are located in non-coding regions (introns).
• SNPs influence traits and diseases.
• 10 pharmaceuticals donated millions to the SNP Consortium.

Genome-Wide Association Studies (GWAS)

• GWAS compare genomic DNA from large samples of cases and controls to identify SNPs correlated with specific traits or diseases.
• Sites differing significantly between cases and controls are validated in independent samples.
• Used to identify links between genetic markers and diseases.

The HapMap Project

• A public database containing over one million common genetic variations (SNPs) from four human populations.
• It was crucial in advancing genome-wide association studies.

Bioinformatics Databases

• GeneBank/DDBJ/EMBL: Nucleotide sequence data
• Ensembl: Human and mouse genome data
• PubMed: Literature references and abstracts
• Swiss-Prot: Protein sequences of known function
• OMIM: Catalog of human genetic diseases

Genome De Novo Sequencing (NGS)

• NGS is used to sequence whole genomes.
• Used for genomic studies using fragments of DNA.
• Steps in the NGS process: fragment and sequence, prepare and sequence reads, remove low coverage regions, break up the contigs and create scaffolds/assemble sequences from contigs and scaffolds, and closing gaps in scaffolds.

Bioinformatics Analysis

• SOAP Alignment, InDel Detection & Annotation, SNP Detection & Annotation, etc.
• Individual re-sequencing, HGMD analysis and Haplotypes construction are examples of optional bioinformatics analyses.

Medical Products and Applications of Biotechnology

• Microarray technology is a method for analyzing the expression of genes in different tissues.
• This technique is applied to cancer research and many other biotech fields.

This quiz covers key topics in bioinformatics, including molecular diagnostics and genetic disease detection techniques. You'll learn about tools like microarrays, amniocentesis, and fluorescence in situ hybridization. Assess your understanding of the application of statistics and computer science in biology.