Genetic Principles: An Overview of Heredity and Mutation, Slides of Medicine

Download Genetic Principles: An Overview of Heredity and Mutation and more Slides Medicine in PDF only on Docsity!

Genetic

Principles

Jason Ryan, MD, MPH

Genetics

Terminology

• Genome
  • DNA contained in nucleus of cells
  • “Hereditary material”
  • Passed to successive generations of cells
• Genes
  • Portions of DNA/genome
  • Code for proteins that carry out specific functions

Chromosomes

Cell Types

• Somatic cells (most body cells)
  • Diploid: two sets of chromosomes (23 pairs)
• Gametes (reproductive cells)
  • “Haploid”: one set of chromosomes

Meiosis

• Gametes (reproductive cells)
  • “Haploid”: one set of chromosomes
  • Produced by meiosis of germ line cells
  • Male and female gametes merge in fertilization
  • New “diploid” organism formed
• Key point: one gene from mother, one from father

Genetics

Terminology

• Allele
  • Alternative forms of gene
  • Many genes have several forms
  • Often represented by letter (A, a)
• Genetic polymorphism
  • Genes exist in multiple forms (alleles)
• Locus (plural loci)
  • Location of allele on chromosome
• DNA → gene → allele → locus → chromosome

Genetics

Terminology

• Wild type gene/allele
  • Common in most individuals
  • Example: A = wild type
• Mutant gene/allele
  • Different from wild type
  • Caused by a mutation
  • Example: a = mutant
  • Individual: AA, Aa, aa

Genetics

Terminology

• Homozygous
  • Two identical copies of a gene (i.e. AA)
• Heterozygous
  • Two different copies of a gene (i.e. Aa)

Genetics

Terminology

• Dominant gene/allele
  • Determines phenotype even in individuals with single copy
  • Often denoted with capital letters
  • Example: Gene has two alleles: A, a
  • Aa, AA all have A phenotype
• Recessive gene/allele
  • Requires two copies to produce phenotype
  • Often denoted with lower case letters
  • Example: aa = a phenotype; Aa and AA = A phenotype

Codominance

• Both alleles contribute to phenotype
• Classic example: ABO Blood Groups
  • A gene = A antigen on blood cells
  • B gene = B antigen
  • O gene = No A or B antigen
• AB individuals
  • Express A and B antigens

Penetrance

• Proportion with allele that express phenotype
• Incomplete penetrance
  • Not all individuals with disease mutation develop disease
  • Commonly applied to autosomal dominant disorders
  • Not all patients with AD disease gene develop disease
• Example BRCA1 and BRCA2 gene mutations

BRCA1 and BRCA

• Genetic mutations that lead to cancer
• Germline gene mutations
• Autosomal dominant
• Not all women with mutations develop cancer
• Implications:
  • Variable cancer risk reduction from prophylactic surgery

Pleiotropy

• One gene = multiple phenotypic effects and traits
  • Example: single gene mutation affects skin, brain, eyes
• Clinical examples:
  • Phenylketonuria (PKU): skin, body odor, mental disability
  • Marfan syndrome: Limbs, eyes, blood vessels
  • Cystic fibrosis: Lungs, pancreas
  • Osteogenesis imperfecta: Bones, eyes, hearing

Two-Hit Origin of Cancer

• Mutations in tumor suppressor genes
  • Genes with many roles
  • Gatekeepers that regulate cell cycle progression
  • DNA repair genes
• Heterozygous mutation = no disease
• Mutation of both alleles → cancer
• Cancer requires “two hits”
  • “Loss of heterozygosity”