Genetics 2 Flashcards
AUTOSOMAL RECESSIVE DISORDER:
which gene is affected by the mutation in cystic fibrosis
the transmembrane conductance regulator (CFTR)
AUTOSOMAL RECESSIVE DISORDER:
what does CTFR gene control
it is a protein chanel + sits in epithelial lining of cells
allows export of chloride ions out of the epithelial cells of the airways
AUTOSOMAL RECESSIVE DISORDER:
what happens if CTFR gene fails
MUCOSTASIS
Cl- not moved across membrane of epithelial cells
build up of sticky mucus which bacterial pathogens invade leading to severe lung disease as bacteria grow on mucus
AUTOSOMAL RECESSIVE DISORDER:
what do sickle cell anaemias and thalassaemias affect
red blood cell (erythrocytes) activity + functionality
AUTOSOMAL RECESSIVE DISORDER:
what are sickle cell anaemia and thalassaemia’s characterised by
abnormalities in the haemoglobin structure
single base mutations in haemoglobin gene affect how beta globin molecules form structural tetramers that carry o2 in red blood cells
AUTOSOMAL RECESSIVE DISORDER:
what does selective pressure in areas where malaria is endemic mean for frequency of sickle cell anaemia and thalassemias
higher frequency than expected in a normal population because having this mutation gives a survival advantage that selects for this mutation (a balanced polymorphism)
heterozygosity leads to increased resistance
AUTOSOMAL DOMINANT DISORDER:
what is dentinogenesis imperfecta
leads to poorly formed dentine and results in early tooth loss
AUTOSOMAL DOMINANT DISORDER:
explain the form of dentinogenesis imperfecta where the DSPP gene (gene for dentin sialophosphoprotein) is affected
C to T substitution in the DSPP gene
DSPP gene = located on chromosome 4 at position 4q12-23
AUTOSOMAL RECESSIVE DISORDER:
what characterises this type of disorder
heterozygous carriers might not show phenotype symptoms / show minor symptoms
only when 2 carriers mate and produce offspring w 2 affected alleles that disease is expressed (reason incest is not permitted - leads to expression of heterozygous genetic diseases)
what is the effect of an autosomal dominant gene on a family
devastating effect because every individual who receives a copy of this affected gene in the offspring is affected by the disease and shows disease symptoms
what is important to realise when determining probabilities from pedigrees
doesn’t mean 50% of offspring all have disease but the probability for each individual offspring to be affected is 50%
AUTOSOMAL DOMINANT DISORDER:
what does huntingtons disease lead to
usually starts in middle age
depression
dementia
involuntary spasms (these are chorea - so aka chorea huntingtons)
AUTOSOMAL DOMINANT DISORDER:
what is the molecular basis of huntigtons
increase in number of repeats of CAG triplet sequence in the dna of a gene linked to the disease
normal people = around 15 copies of this repeat sequence
huntingtons sufferers = 36+
AUTOSOMAL DOMINANT DISORDER:
in huntingtons what is the correlation between number of copies of repeating sequences and the disease symptoms
the more copies = the move severe the symptoms
example of a gene dosing effect
which type of disease can be easily observed from a pedigree + identified by pedigree analysis and why
x-linked genetic disease (sex-linked)
look at pedigree and realise only males are affected
in x-linked disease what may females be
carriers that may not express symtpoms
in x-linked disease what will there be NO evidence of
no male carriers and no father to son transmission of the condition because disorder is located on the x chromosomes and male offspring cannot inherit x chromosome from father as they get Y from their father
give 2 examples of x-linked disorders in humans
1) haemophillia
2) amelogenesis imperfecta
X-LINKED DISORDER:
what is haemophillia
impaired blood clotting (mutation of important blood clotting factor) and bleeding cant be stopped quickly
have to take recombinant blood clotting factors
higher frequency where interbreeding has occured (european royal families, russian princes)
X-LINKED DISORDER:
what is amelogenesis imperfecta
poorly formed enamel and defects on teeth because of mutations in amelogenin / AMELX gene for the tooth enamel matrix protein
expression of the disease is patterned leading to an effect of striped teeth (stripes of functional enamel alternated with stripes of affected enamel)
explain lyonisation / X-inactivation
mosaic like expression of a disease in females w x-linked disorders
1 X chromosome in females gets inactivated in every body cell but in a random pattern (so random pattern of distribution and also to striped teeth effect in amelogenesis imperfecta because some ameloblasts will produce functional amelogenin + others wont depending on lyonisation)
as 1 chromosome is randomly inactivated, only 1 of the alleles is expressed bc females have 2 x chromosomes (one has defective allele and other has unaffected allele)
can lead to sexually dimorphic phenotypic appearance of these disorders
what are polygenic / multifactorial genetic disorders
multiple mutated genes contribute to formation of disease
environmental / external factors can make these diseases more severe
how do genes act in polygenic / multifactorial genetic disorders
many involved in disease process
others supress / modify it (modifying genes / protective factors)
what do polygenic / multifactorial genetic disorders make difficult due to their complexity
genetic analysis and pedigree analysis
