Mendelian Inheritance and mitcohcondrial genetics Flashcards
What contributions lead to human disease?
Genetic and environmental
What are the classification of genetic disorders?
Single gene Multifactorial Chromosome Mitochondrial Somatic
How can gain or loss of gene function come about?
But mutations in DNA
What is a genotype?
A pair of alleles at a locus
What are some single gene disorders?
Autosomal Dominant
Autosomal Recessive
X-linked
What is autosomal dominance?
A dominant allele (mutation) will determine a
phenotype when only one copy is present
in the genome.
What are some autosomal dominant disoders?
FAP - Familial Adenomatous polyposis
Achondroplasia - Dwarfism
Marfan Syndrome
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
What phenotypes are generally encountered in autosomal dominant families?
Wild type and heterozygous mutant
Homozygous are usually very severe and often not seen
What type of disorder is cystic fibrosis?
Autosomal recessive
What are the features of cystic fibrosis?
Problems with: Lungs Pancreas Sweat glands Sometimes other organs
Encodes a transmembrane protein that transports chloride ions, Mutations disrupt this chloride conductance
Affects 1/2500 people
What are some other autosomal recessive disorders?
Primary Haemochromatosis Cystic fibrosis Sickle cell disease Phenylketonuria Ataxia Telangiectasia
What causes Ataxia Telangiectasia?
Biallelic mutation of ATM gene
Mutation can occur at any point in the gene and produces the same effect
What are autosomal recessive disorders?
A recessive allele has no effect on the organism’s
phenotype if only one copy of the allele is present
in the genome.
You could be carrying a mutation in a gene and be
totally unaware of this- case for carriers of recessive
Diseases
What are the features of autosomal recessive disorders?
Only seen in one generation
Both parents are normally carriers
What is the origin of recessive mutations?
Most random mutations will either be neutral
or inactivating.
Default state of mutations is therefore recessive.
In the homozygous state there will be no function
and consequences will be seen in clinical state.
In the heterozygous state there will be no effect
of the allele on the organism.
How does dominance of a mutation occur?
Dominant disorders outnumber recessive. Occur via molecular basis: Reduced gene dosage (haploinsufficiency) Increased gene dosage Altered expression of mRNA Increased protein activity Dominant negative effects Altered structural proteins Gain of new function
What are the features of X-linked inheritance?
- Incidence of the trait is much higher in males than females
- The gene responsible for the condition is transmitted from an affected man through all his daughters.
- The gene is never transmitted from father to son.
- Sons always inherit their X chromosome from their mother.
Give an example of a disease that is X-linked inherited?
Haemophilia
Duchenne Muscular Dystrophy
What is multifactorial inheritance?
Multifactorial inheritance disorders are caused by a combination of small inherited variations in genes, often acting together with environmental factors.
Heart disease, diabetes, and most cancers are examples of such disorders.
Behaviors are also multifactorial, involving multiple genes that are affected by a variety of other factors.
Genetic contribution to behavioral disorders such as alcoholism, obesity, mental illness and Alzheimer’s disease.
How are chromosome disorders caused?
Chromosome disorders are caused by an excess or deficiency
of the genes that are located on chromosomes, or by structural changes within
chromosomes. Down syndrome, for example, is caused by an
extra copy of chromosome 21 (trisomy 21), although no
Individual gene on the chromosome is abnormal.
Why is the frequency of mitochondrial disorders high?
MtDNA has a much higher proportion of
coding DNA (93%) compared with about 3% in nuclear
DNA. Remember, however there is still about 100Mb
nuclear DNA.
Higher mutation rate in mtDNA. Rate at which
mutations are fixed in mtDNA is about 10x higher than/.
in nuclear DNA.
How are mitochondrial mutations fixed?
the mitochondrial molecule has to replace all other molecules to return to homoplasmy.
What are mitochondria deficient in?
Recombination
