Intro And Modes Of Inheritance Flashcards
How many chromosome and genes do we have?
46 (23 pairs)
25000 genes
22 aoutosomal pairs and one pair of sex chromosomes
Male: XY
Female: XX
What is mitochondrial DNA?
Around 16500 base pairs
Codes for 15 proteins, rRNA and tRNA
All derived from mother
But most mitochondrial proteins are encoded by the cell genome
What are different versions of a gene called?
Alleles
What are Hetero and homozygous?
Heterozygous
Two different alleles
Homozygous
Two identical alleles
What is the position of a gene called?
Locus
What are three types of human genetic disorder?
Single gene disorders
Chromosomal disorders
Complex disorders
What are single gene disorders?
Most common genetic disorders effect (1/500) people But there are >5500 types
But overall they affect a large number of people (1.5%)
Affect all body systems so concern all specialities
Large health burden
What are chromosomal disorders?
Affect 1/150 live births
Occur when a chromosome is damaged during formation of sperm or egg or during early development of the embryo
What are complex disorders?
Common diseases
Result of genetic and environmental factors
E.g obesity and type II diabetes
What do autosomal dominant diseases mean?
A characteristic is dominant if it manifests in a heterozygote
Refers to phenotype
Single gene disorders
Affects multiple generations
Us usually one affected parent at least
1/2 chance of being affected
Males and females affected equally
Vertical pedigree pattern
Why are some genes dominant? (Simple)
Certain alleles activate genes, others leave them inactivate
E.g. eye colour
Gene responsible is OCA-2
Active —> melanin —> brown
Inactive —> no melanin —> blue
Therefore an allele that causes OCA-2 to be active overrides the lack of melanin
What are the three ways in which a single gene disorder is dominant?
Gain-of-function
Dominant negative effect
Insufficient
What does gain of function mean?
A gene now makes a protein with a new function
Which isn’t usually seen
E.g. longer lifespan of protein or new location
What does a negative dominant affect mean?
The mutated form interferes with the activity of proteins it binds
E.g. in dimers or multimers which reduces activity of other proteins in the multimer
What does insufficiency mean?
Mutant in one gene results in 1/2 the amount of a protein
This is not a sufficient amount for normal function
What is a carrier of a disease?
Only in autosomal recessive
Lost a single copy of a gene but the remaining one is sufficient for normal function
What are some properties of autosomal recessive disorders?
Parent and children normally unaffected
One or more siblings affected
1/4 chance of being affected (two carrier parents)
Males and females equally affected
Horizontal pedigree pattern
What do consanguineous marriages mean in terms of autosomal recessive disorders?
Elevate the risks of these diseases
1/5 of the wotrlds preference for marriage includes this
Rarer diseases with a lower gene frequency have a much higher relative risk
Disease gene frequency (q) 0.01 0.001
Relative risk in 1st cousins 6.25 62.5
How do autosomal recessive dosorders cause loss of function?
Work less well
Degraded faster
Inadequate amounts
What are the sex chromosomes?
X
1000-1300 genes
Y
150 genes
Men: XY
Women: XX
What are some points about X linked recessive disorders?
Affect mainly males (essentially dominant)
Affected boys may have affected uncles
Parents and children are commonly unaffected
Children of a man with one: boys will be healthy, girls will all be carriers
I’m some cases female characters can exhibit subtle signs
What are some properties of x linked dominant diseases?
Similar pattern to autosomal dominant
But: all daughter but no sons of a an affected father are affected
All children of an affected mother can be affected
Often milder conditions in females than males due to random x inactivation
Some males affected by these diseases are not viable so these diseases are only present in females
What are some features of y linked disorders?
Only affect males Very rare All sons of a father are affected Vertical pedigree pattern So few diseases because of limited number of genes in the Y chromosome
How are mitochondria inherited in humans?
From the mother
So all diseases caused by mutations in mitochondrial DNA are maternally inherited
Vertical pedigree pattern
All children of an affected mum
Will be affected
None from an affected dad
However all mitochondrial diseases are very variable within a family
Why do mitochondrial diseases show so much variability in expression?
Heteroplasmy - mitochondria have several copies of genome, not all are mutated
They only express the disease above a threshold
Mutated genes can be gained or lost in binary fission
Random segregation during cell division, different numbers of diseases mitochondria will be passed into daughter cells
Must reach a threshold to develop symptoms
Most mitochondrial diseases develop with age due to accumulation of mutant mitochondria
