Human Genome Project & Genetic Factors in Smoking

Human Genome Project

• Primary purpose: To sequence the euchromatic regions of the genome.
• Officially declared complete in 2003.

CHRNA5 Gene Mutation

• 35% of Europeans carry a mutation associated with nicotine dependence.

Nicotine Metabolism Genes

• CYP2A64C gene variants affect nicotine metabolism speed.

Nicotinic Acetylcholine Receptor

• CHRNA5-A3-B4 cluster contributes to severe nicotine dependence.

Hungarian Roma Population Smoking Rates

• 53% of the Hungarian Roma population are heavy smokers compared to 31% of the general population.

Early Onset Smoking Gene

• DAT (rs27072-A) gene polymorphism linked to early smoking.

FTO Gene Significance

• Influences fat mass and obesity.

Human Genome Size

• 3 billion base pairs.

Public Health Genomics Focus

• Identifying the interaction of genes and lifestyle on population health and diseases.

Prenatal Genetic Diagnosis Techniques

• Amniocentesis, CVS, cordocentesis.
• PCR, SNP arrays, microarrays, ultrasound.

Expanded Carrier Screening (ECS)

• Screens carriers for severe childhood-onset diseases.

NIPT Availability in Hungary

• Available in 2012.

Non-coding Regions Percentage

• 80% of the human genome is non-coding.

Alcohol Metabolism Gene

• ALDH2 gene associated with alcohol metabolism.

Pharmacogenomics Role

• Understanding drug response based on genetics.

Codon Definition

• A triplet of bases coding for an amino acid.

Vertebrate Genomes Project

• Aim to sequence at least one genome per vertebrate genus.

Fluorescence In Situ Hybridization (FISH)

• Uses labeled probes to locate DNA sequences.

Human Genome Project Sequencing Method

• Sanger sequencing.

PCR Error Sources

• Mispriming, contamination.

Capillary Electrophoresis in Sequencing

• Separates DNA fragments by size.

Severe Nicotine Dependence Mutation

• CHRNA5 rs1051730.

SNP Percentage

• 0.1% of the human genome are SNPs.

Human Gene Number

• ~22,000 genes.

Degenerate Genetic Code

• More than one codon encodes a single amino acid.

Nicotine Receptor Sensitivity Gene Cluster

• CHRNA5-A3-B4 associated with nicotine receptor sensitivity.

Prenatal Chromosomal Anomalies Marker

• Non-invasive prenatal testing (NIPT).

Euchromatin vs. Heterochromatin

• Euchromatin is transcriptionally active; heterochromatin is inactive.

Gene Annotation Method

• Genome browsers (e.g., UCSC).

Melanoma Susceptibility Gene

• MC1R.

Telomere DNA Type

• Repetitive DNA.

DNA Double Helix Discovery Year

Human Genome Project Goals

• Identify all 22,000 genes in human DNA and sequence 3 billion base pairs.

Comparative Genomic Hybridization (CGH) Techniques

• Fluorescent labeling of DNA samples, DNA microarrays.

Nicotine Dependence Genes

• CHRNA5, DRD4,

SNP Array Information

• Single nucleotide polymorphisms, chromosomal copy number variations.

Risk Factors for Disease

• Genetic polymorphisms, lifestyle choices, environmental exposures, family history.

CRISPR-Cas9 Gene Editing Benefits

• Correcting genetic disorders, enhancing agricultural crops, accelerating drug development.

Epigenetic Change Factors

• Dietary habits, exposure to pollutants.

Polygenic Risk Scores Use in Practice

• Predicting susceptibility to complex diseases, personalizing lifestyle interventions.

Single-Cell Sequencing Advantages

• Analyzing gene expression at the cellular level, detecting rare cell populations, determining chromosomal abnormalities.

Environmental Mutagenesis Trigger

• Ultraviolet radiation, tobacco smoke, pesticides.

GWAS Result Factors

• Population size, genetic heterogeneity, environmental considerations, study cohort selection.

Telomere and Cellular Aging

• Protect chromosomes, shorten with each cell division.

Transcriptomics Tools

• RNA-seq, microarrays.

Genetic Drift Characteristics

• Random changes in allele frequency, stronger effects in smaller populations.

Linkage Disequilibrium Studies Information

• Association between genetic variants.

Gene Pathways Commonly Deregulated in Cancer

• Cell cycle regulation, DNA repair mechanisms, chromatin remodeling.

Next Generation Sequencing (NGS) Features

• High-throughput data generation, reduced sequencing costs, single-molecule resolution.

Cytogenetic Analyses Focus

• Chromosomal translocations, aneuploidy.

Epigenetic Change Reversal Methods

• DNA methylation inhibitors, histone deacetylase inhibitors, and CRISPR gene editing.

Proteogenomics Application

• Linking gene expression to protein functions, understanding disease mechanisms, designing targeted therapies.

Gene Therapy Limitations

• Short-term effects, challenges in gene delivery, and risk of insertional mutagenesis.

Bioinformatics Molecular Markers

• Ribosomal RNA genes.

Gene-Environment Interaction Research Focus

• Cardiovascular diseases, diabetes, chronic respiratory diseases.

Ethical Issue in Public Health Genomics

• Genetic discrimination, genetic data privacy, and equity in access to genomic services.

Epigenetics Contribution to Public Health Genomics

• Understanding gene-environment interactions, identifying modifiable genetic variations, and developing targeted lifestyle interventions.

Genomic Epidemiology Study Aspects

• Representativeness of study cohorts, robust statistical methods, integration of genomic and environmental data.