Public Health Genetics and Molecular Biology Notes

Public Health Genetics

Public health genetics studies genetics and genomics at a population level. Genetics is broadly influential in public health, with its influence expected to increase.

Links between genetic mutations and disease help identify at-risk individuals and develop personalized treatments. Key areas include inheritance patterns and gene-environment interactions.

Elementary Human Genetics

Genetics studies inheritance; genomics studies all genes at the DNA, protein, cell, or tissue level.

DNA and Chromosomes

  • Humans have 23 pairs of chromosomes per cell: 22 autosomal pairs and 1 pair of sex chromosomes (XX in females, XY in males).

  • Each chromosome carries genes (DNA segments encoding a specific protein).

  • The human genome contains roughly 20,000 to 25,000 protein-coding genes.

  • Mitochondrial DNA also codes genes, inherited from the mother.

DNA Bases and Codons

DNA consists of four bases: Adenine (A), Thymine (T), Cytosine (C), Guanine (G).

A codon (triplet nucleotide sequence) represents instructions for a specific amino acid. Only about 2% of DNA is protein-coding (exons); up to 18% comprises regulatory sequences.

Gene Expression

Gene expression is the process where DNA is used to make proteins. DNA is transcribed into RNA, then translated into amino acids, which form proteins. Different cells have different functions because different genes are expressed in different cell types.

Variations in Genetic Material

Most (99.9%) of human genetic material is identical across individuals; 0.1% differs, accounting for individual characteristics and disease propensity.

Reasons for differences:

  1. Genes are shuffled during meiosis.

  2. Mutations or polymorphisms occur in the DNA sequence.

  3. Epigenetic changes affect gene expression.

A genetic polymorphism is a variation in the genetic sequence present in at least 1%–2% of the population. Gene mutations are rarer, harmful changes in DNA sequence. Mutations in gamete-producing cells can be passed to offspring.

Inherited Diseases

Most diseases have genetic and environmental risk factors, but some are caused by single-gene mutations or chromosomal disorders.

Types of Inherited Diseases

  • Multifactorial diseases: Multiple genetic and environmental factors (e.g., CHD, diabetes, cancers). Genetic variants increase risk but do not guarantee occurrence.

    Example: BRCA1 mutation increases breast cancer risk.

  • Single-gene disorders (Mendelian disease): One altered gene causes the illness (e.g., Huntington’s disease, cystic fibrosis). Classified as autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, or Y-linked.

  • Chromosomal disorders: Affect whole chromosomes or large parts (e.g., Down’s syndrome, Charcot–Marie–Tooth disease). Include numerical disorders and structural abnormalities.

Basic Genomic Concepts

Key concepts include patterns of inheritance, penetrance, genotype/phenotype differences, polygenetic disorders, gene-environment interactions, and the role of genes in health and disease.

Genotype and Phenotype

Individuals carry two copies of each autosomal gene (alleles). The set of alleles is the genotype, and expressed characteristics are the phenotype.

  • Homozygous: Two identical gene copies; individual displays the phenotype.

  • Heterozygous: Different gene copies; expression depends on dominant allele.

The presence of a genotype does not guarantee the phenotype due to incomplete penetrance, multiple mutations, multiple genes, gene-environment interactions, or epigenetic changes.

Patterns of Inheritance

Inheritance is Mendelian or non-Mendelian.

  • Mendelian inheritance: Autosomal or sex-linked, and dominant or recessive.

  • Non-Mendelian inheritance: Multifactorial (polygenic disorders and gene-environment interactions). Mitochondrial genes are maternally inherited.

Mendelian Inheritance Patterns (Table 2D.2)

  • Autosomal dominant: One abnormal gene copy causes illness (e.g., Huntington’s disease).

  • Autosomal recessive: Both copies must be abnormal (e.g., cystic fibrosis).

  • X-linked recessive: Mutation on the X chromosome; males more affected (e.g., hemophilia).

  • X-linked dominant: One mutated gene on the X chromosome causes the condition (e.g., Coffin–Lowry syndrome).

  • Y-linked: Rare; affects males (e.g., male infertility).

Penetrance

Penetrance is the proportion of people with a given genotype that express its phenotype.

Polygenic Disorders

Polygenic disorders involve multiple gene variants increasing disease susceptibility. Patterns are complex, and gene interactions are poorly understood. Identifying these genes may help in understanding disease, predicting risk, and targeting prevention, health promotion, and treatments.

Gene-Environment Interactions

Most common diseases result from genetic susceptibility factors interacting with environmental risks. Individuals inherit susceptibility, modified by environmental factors. Epigenetics may explain these interactions.

Genetic Disease Prevention

Avoiding particular environmental conditions can prevent some genetic diseases (e.g., PKU).

Health Promotion and Genetic Disease

Studying gene-environment interactions helps identify high-risk individuals and understand which environmental factors increase risk, targeting health promotion and disease prevention.

Genes in Health and Disease

Pharmacogenomics uses genetic characteristics to understand pharmaceutical treatment effectiveness. Gene therapy inserts genetic material into cells to treat diseases.

Disease in Relatives

Relatives may want to know if they carry an abnormal gene. Predictive genetic testing and individual carrier testing are relevant but raise ethical issues.

  • Predictive genetic testing: For highly penetrative genetic diseases (e.g., Huntington’s disease).

  • Individual carrier testing: For asymptomatic individuals with affected relatives (e.g., cystic fibrosis).

Combining risk alleles could be used for risk stratification and screening.

Control of Disease

Control measures may include: preimplantation genetic diagnosis, antenatal testing, screening, prophylactic surgery, treatment to reduce risk, and genetic counseling.

Molecular Biology

Molecular biology studies biological processes at a molecular level, analyzing DNA, RNA, and proteins. It overlaps genetics and biochemistry.

Molecular Biological Techniques

Techniques include restriction enzymes, PCR, and DNA sequencing.

Implications for Public Health

Advances offer potential for targeted health promotion, screening, and medical treatment based on genetic profiles. Genomic profiling is used in cancer medicine.

Molecular Biology Applied to Microbiology

Molecular biology is crucial for pathogen identification and understanding microbial function.

Pathogen Genetics

Examples of genes conferring virulence: reverse transcriptase in retroviruses, plasmids conferring antibiotic resistance, and genes enabling rapid exchange of surface antigens.

Pathogen Identification

Sequenced genomes of pathogens aid in identifying organisms and strains, understanding disease etiology, detecting trends, and linking infectious disease cases to outbreaks.