L15: Patterns of Inheritance Flashcards
What two components contribute to human disease?
Environmental and genetic factors
What is the spectrum of genetic diseases?
Genetic diseases range from those caused by a single gene mutation (e.g., Duchenne muscular dystrophy) to those influenced by both genetic and environmental factors (e.g., spina bifida), and those primarily caused by environmental factors with minimal genetic influence (e.g., scurvy, tuberculosis)
Name some diseases caused by genetic factors
- Duchenne muscular dystrophy
- Haemophilia
Name some diseases caused by environmental factors
- Tuberculosis
- scurvy
Name some human diseases caused by both environmental and genetic factors
- Spina bifida
-diabetes
-ischaemic heart disease
What characterises genetic factors in causing human disease?
- Rare
- genetics simple
- unifactorial
- high recurrence rate
What characterises environmental factors causing human disease?
- Common
- Genetics complex
- Multifactorial
- Low recurrence rate
What can mutations in genes cause?
Loss or gain of gene function
What ways can mutations affect genes?
- Involve a single gene (Mendelian inheritance)
- Involve a chromosomal segment (or whole chromosome) which affects thousands of genes
- Involve several genes acting with environmental influences (multifactorial inheritance)
What is multifactorial inheritance?
- Involves multiple genes and environmental factors
- Examples include spina bifida, where both genetic susceptibility and environmental influences (like maternal health) contribute to the condition.
- Variants in genes causing alteration in function
What are mitochondrial disorders?
Generally affect organ systems with high energy requiments
What are chromosomal disorders?
- Caused by mutations or abnormalities in large segments of chromosomes, which may involve hundreds or thousands of genes (imbalance causes alteration in gene dosage)
- Excess or deficiency of genes or structural changes in chromosomes
- Typically result in syndromes with multiple symptoms affecting various systems in the body
What are somatic disorders?
Cause cancer,inactivation of both alleles (two’hits’ ) of a gene involved in growth
Where are genes controlling structure and function of mitochondria found?
Both mitochondrial and nuclear DNA
What are single-gene disorders?
Single-gene disorders are caused by mutations in one gene, often resulting in the loss of gene function. They can follow patterns of inheritance such as autosomal dominant, autosomal recessive, and X-linked
What is a genotype?
A pair of alleles at a locus
What is a phenotype?
The observable characteristics of an individual resulting from the interaction of its genotype with the environment
What is autosomal dominance?
- What we call a dominant allele (mutation) will determine a phenotype when only one copy is present in the genome of the individual
- Not from the sex chromosomes (not the X or Y chromosomes)
Give some examples of autosomal dominant disorders
- Achondroplasia - dwarfism (mutation of FGFR3 gene)
- Marfan Syndrome - connective tissue disorder-patients very tall (mutation of FBN1 gene)
- Neurofibromatosis
What are the features of autosomal dominant inheritance?
- Affected individuals in every generation
- Male and female equally likely to be affected
- Inherited from one OR other affected parent, BUT can be a new mutation e.g. neurofibromatosis, achondroplasia - known as a de novo mutation
What type of mutant phenotypes are in autosomal dominant families?
Usually only the wild type and heterozygous mutant phenotypes encountered
Can homozygous mutant phenotypes occur in autosomal dominant disorders?
- Very rare and not seen
- Usually very severe phenotypes which are often lethal
What is autosomal recessive inheritance?
- Both copies of the gene must be mutated for the disease to manifest
- Carriers (with one mutated allele) typically do not show symptoms
What is the best example of a autosomal recessive disease?
Cystic fibrosis
What are the features of cystic fibrosis?
- Affects the lungs, pancreas, sweat glands, and sometimes other organs
- 4% of caucasians are carriers of CF mutation
What effect does cystic fibrosis have on the body?
- Encodes a transmembrane protein (CFTR) that transports chloride ions
- Mutations disrupt this chloride conductance
How is cystic fibrosis inherited?
- Follows autosomal recessive inheritance. Both parents must be carriers for the disease to manifest in their child
- The chance of having an affected child is 1 in 4 if both parents are carriers
What are examples of recessive disorders?
- Hemochromatosis: A disorder affecting iron metabolism, leading to organ damage.
- Sickle cell disease: Caused by mutations in the beta-globin gene, leading to severe anemia.
- PKU (Phenylketonuria): A metabolic disorder that can cause brain damage if not managed early with a special diet.
What is the carrier frequency of sickle cell disease in African populations? What is the molecular cause?
- Approximately 1 in 12 in African populations, leading to an incidence of 1 in 600 for the disease in those populations
- A mutation in the beta-globin gene, which leads to abnormal hemoglobin production, resulting in sickled red blood cells that can block blood flow and cause severe anemia
Why do recessive genetic disorders often have carriers? How they be identified?
- Carriers typically do not show symptoms, because the normal allele compensates for the mutated one, but they can pass the mutation onto their offspring
- Genetic testing can identify them
- They have one normal and one mutated allele for a given gene