Inheritance Flashcards
What can mutations involve?
Can involve:
A single gene
A chromosomal segment which affects thousands of genes.
Several genes acting with environmental influences.
What are single gene disorders?
Mutations in single genes by:
Autosomal dominance
Autosomal recessive
X-linked
What is a genotype?
A pair of alleles at a locus
e.g. AA, Aa, aA, aa, which then gives the phenotype.
What is a dominant allele?
A dominant alelle will determine a phenotype when only one copy is present in the genome of the individual.
What are autosomal chromosomes?
Chromosomes number 1-22, not the sex chromosomes.
What are examples of autosomal dominant disorders?
Achondroplasia - dwarfism, FGFR3 gene.
Marfan Syndrome - FBN1
Neurofibromatosis
What are features of autosomal dominant inheritance?
Affects every generation.
Male and female equally likely to be affected.
Inherited from one or other affected parent.
Can arise from a new mutation.
Why are heterozygous individuals seen only in autosomal dominant families?
The homozygotes are usually very severe phenotypes and are lethal.
What are autosomal recessive disorders?
A recessive allele has no effect on the organism’s phenotype if only one copy of that allele is present in the genome.
So there are carriers of recessive diseases.
What are examples of autosomal recessive disorders?
Primary haemochromatosis
Cystic fibrosis
Sickle cell disease
Phenylketonuria
Ataxia telangiectasia
What is cystic fibrosis?
Encodes transmembrane protein CFTR that transports Chloride ions.
Mutations disrupt chloride conductance.
How is the difference between a dominant and recessive mutant allele identified?
If the residual amount of normal gene product is sufficient to perform its function then the mutant allele and its disorder is recessive.
If insufficient, then it is dominant.
How does dominance of a mutation occur?
Reduced or increased gene dosage
Altered expression of mRNA
Increased protein activity
Dominant negative effects
Altered structural proteins
Gain of a new function.
What is reduced gene dosage?
This is where expression from one normal allele is not sufficient for function.
What is increased gene dosage?
Due to the presence of 3 copies of mutant gene.
E.g. Trisomy 21 - down syndrome
Marie-Tooth Type 1
Gene amplification
What is altered expression of mRNA?
Due to loss of control of regulation of mRNA expression.
Hereditary persistence of fetal haemoglobin.
What is increased protein activity?
Increased half life or loss of normal inhibitory regulation
What are dominant negative effects?
In the heterozygous state these mutants antagonise the activity of the remaining normal allele.
They are often multimeric proteins.
What are altered structural proteins?
A mixture of normal and abnormal structural alterations will disrupt the whole structure.
E.g. Fibrillin in Marfans affects myosin heavy chains causing cardiomyopathy.
What is gain of new protein function?
Chromosome translocations giving rise to new genes/proteins.
e.g. fusion proteins - in chronic myeloid leukaemia.
What are the characteristics of X linked inheritance?
Higher incidence in males than females.
The gene responsible for the condition is transmitted from affected man to all daughters.
Never transmitted from father to son - sons always inherit X chromosome from mother.
What is an example of X-linked inheritance diseases?
Duchenne Muscular Dystrophy
What are multifactorial diseases?
Variants in genes causing alteration in function, often acting with environmental factors.
Behaviours are also mutlifactorial - involving mutliple genes affected by many factors.
What are examples of multifactorial inheritance?
Heart disease, diabetes and most cancers.
There is genetic contribution to behavioural disorders such as alcoholism, obesity, mental illness and Alzheimers.
