Wk.5 L2 - The Influence of Genetics on Disease Flashcards
LO
- Develop an understanding of the scope and impact of genetic disorders in human disease across a lifespan
- Describe the three main categories of human genetic disease and provide relevant examples of these disorders
- Describe the 3 main patterns of single gene disorder inheritance (autosomal dominant, autosomal recessive and X-linked) and provide representative examples of each
- Provide brief examples of the range of molecular mechanisms underlying the categories of human genetic disease
Scope and impact of genetic disorders
- Affects ~8% of population
- Up to 50% early miscarriages have an underlying chromosomal abdormality
- 1% of all newborns have a gross underlying chromosomal abnormality
- 5% of people before 25 develop a serious illness with a significant genetic basis
Classification of genetic disorders
- Chromosomal disorders
- Single Gene Disorders
- Polygenic/ Multifactorial disorders
Chromosomal disorders
Structural or numerical alterations in autosomal or sex chromosomes
Numerical Alterations:
Gain- Down Syndrome
Lose- Turner Syndrome 45X
Structural Alterations:
Somatic Translocation
Germline Deletion
Major impact before birth, affects health throughout childhood and early life
Single Gene Disorders
AKA Mendelian/ Monogenic Disorders
3 Patterns of inheritance:
1. Autosomal Dominant
2. Autosomal Recessive
3. X-linked
Affects individuals from perinatal period to adulthood with a peak in mid-childhood
- Sickle Cell Aneaemia
Polygenic/ Multifactorial Disorders
Polymorphisms:
Presence of 2 or more varients of a specific DNA sequence
Typically present later in life, except for developmental anomalies requiring early multidisciplinary care
- Type 2 Diabetes
- Ischaemic Heart Disease
Complex Multigene disorders (polygenic)
Multiple polymorphisms are inherited, each with a modest effect and low penetrance which coinherited and cause disease when combined with environmental effects
- Familial Combined Hyperlipidemia
Single gene disorders - Autosomal Dominant
- Only 1 copy of a gene with a pathogenic varient is needed to impact the individual
- Each child has a 50% chance of being affected, mild or severe
- Males and femals impacted same
Marfan Syndrome
Single gene disorders - Autosomal Recessive
Largest category of SGD
- Person must have pathogenic varient in both copies of genes
- Cariers with 1 recessive varient are often asymptomatic
Cystic Fribrosis
PKV
Single gene disorders - X-linked
- Pathogen varient is on X chromosome
- If son has the varient he has the disease
- Daughter can have it, but also can be asymptomatic
Colour blindness
Fragile X-syndrome
Molecular mechanism of SGD
Mutation:
- Permanent change in the DNA.
- Affected germ cells are transmitted
to the progeny and can give rise to inherited
diseases
Mutation can occur in a coding or non-coding sequence of DNA
- Point
- Insertion
- Deletion
- Copying number changes, triglyceride repeats and alterations in non-coding RNA
