Molecular and Biochemical Genetics

From Iusmgenetics

Contents 1 Molecular and Biochemical Genetics 1.1 Objectives 1.2 Review your fundamentals 1.3 Dominants 1.4 Achondroplasia 1.5 Osteogenesis imperfecta

Molecular and Biochemical Genetics

Objectives

• Important terms:
  • "Incomplete" dominance or "semi-dominant": homozygous individuals have a worse manifestation than heterozygous individuals (achondroplasia).
  • "Distinct disorder": consistent clinical and radiological findings.
• Important concepts:
  • Types of mutations:
    • Missense: changed amino acid
    • Nonsense: introduced stop codon
    • Neutral / silent: no amino acid change
    • RNA splicing: gain or loss of splice site
    • Regulation mutation: affects gene regulation
    • Indels: gain or loss of one or more bases; leads to frameshift if not a multiple of 3
    • Repeat expansion: repeated segment (usually 3 bases) expands as nucleotide copy / repair mechanisms get hung up
  • Haploinsufficiency:
  • Dominant-negatie effect:

• For individual diseases, know: clinical features, mode of inheritance, genes involved / gene defect, pathogenesis, treatment (sometimes)

Review your fundamentals

Dominants

• Dominant disease are defined as those manifested when only one allele is mutated.
  • Recall that some diseases can be both dominant and negative because of allelic heterogeneity and locus heterogeneity.
• There are multiple ways we describe a single allele causing disease:
  • Qualitative effects: the protein product gains a function.
  • Quantitative effects: the protein product is broken.
  • Combination of qualitative and quantitative.
  • Others
• It is important to understand the disease pathogenesis in order to think wisely about treatment.

Achondroplasia

Osteogenesis imperfecta