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
what else may be involved in expression of these diseases
factors other than genes
what has finding out more about the human genome + its relation to disease enabled
more disorders not previously thought to be genetic now known to have a genetic component / basis contributing to difference in expression + susceptibility
genetic disorder with multifactorial genetic component:
give 3 congenital disorders of this nature
1) spina bifida
2) cleft lip + palate
3) congenital heart disease
genetic disorder with multifactorial genetic component:
give 4 late onset disorders of this nature
1) rheumatoid arthritis
2) multiple sclerosis
3) diabetes mellitus
4) epilepsy
genetic disorder with multifactorial genetic component:
give 4 psychiatric disorders of this nature
1) manic depression
2) alcoholism
3) alzheimers
4) schizophrenia
genetic disorder with environmental component:
give 3 neoplasis disorders of this nature
1) oral cancer
2) breast cancer
3) congenital heart disease
genetic disorder with environmental component:
give 3 cardiovascular disorders of this nature
1) hypertension (high BP)
2) multiple sclerosis
3) epilepsy
genetic disorder with environmental component:
give 3 neuro-degenerative disorders of this nature
1) diabetes mellitus
2) alcoholism
3) alzheimers
genetic disorder with environmental component:
what has evidence on oral cancers shown and how is it multifactorial
formed because of genetic background and multiple genes contribute to susceptibility.
very aggressive and poor prognosis.
multifactorial because tobacco, alcohol can exacerbate it or increase probability of developing / expressing it
genetic disorder with environmental component:
how is genetic analysis helpful and give an example where it may help
can identify at risk individuals and encourage them to change their lifestyle = reducing disease incidence
hypertension (high BP) = modify by lifestyle changes like avoiding stress
what measures would help reduce onset and incidence of disease
better public health measures
education
multi-factorial disease w/ potential polygenic background:
what is periodontal disease
chronic disease leading to erosion of tissues supporting teeth (bone, gum, connective tissue) and tooth loss
multi-factorial disease w/ potential polygenic background:
what was previously thought about perio disease
solely caused by bacteria
microbiota / microbiome composition = result of poor oral hygiene
multi-factorial disease w/ potential polygenic background:
what became evident about perio disease with advances in oral healthcare
individuals with good oral health still develop it
other factors involved ie…
1) altered response to infection = increase severity of disease (like in autoimmune disorders)
2) genes acting as genetic modifiers of the periodontal inflammatory response
multi-factorial disease w/ potential polygenic background:
what happens in periodontal disease expression in different individuals depending on individual genetic background
disease initiating factors (ie bacterial pathogens)
individual genetic response
so different expressions of disease severity
each responds differently to presence of pathogens in oral cavity
multi-factorial disease w/ potential polygenic background:
why may periodontal disease severity be reduced over time
presence of protective alleles
individuals who have susceptibility genes will be affected more severely
what types of methods are used for identification of diseased genes + genetic component determination in specific types of disease
molecular methods
what 2 types of study can be observed to determine genetic component
family studies (ie pedigrees)
twin studies
what do family studies give an idea of
if a disease is due to genetic factors
number of people w same disorder gives indication that observed disease has genetic component
what do twin studies give an idea of
which components of a disease are
a) genetically determined
b) environmental
(nature vs nurture)
what type of twins are used in twin studies and why
monozygotic (IDENTICAL)
same genetic makeup
how do we find what the underlying genetic defects responsible for inherited disorders are at a molecular level
lab procedures for looking at genes
what is the first used, lowest resolution procedure and what are these
linkage analysis
linkage is the tendency of 2 genes/genetic markers to be inherited together bc of their closeness on the same chromosome
molecular family studies giving idea of position of gene
determine which chromosome the genetic detect sits on by following the inheritance of known genetic markers that we can map to different chromosomes (assign chromosomal location)
find mapped linkage marker which always gets inherited along the genetic disease
list 5 more refined and higher resolution tools used after linkage analysis to see where gene is located and the change on the molecular level / finding genes responsible for disorders / traits
1) southern blotting technique (techniques based on dna hybridisation)
2) PCR
3) nucleotide (dna) sequencing
4) gene chips / microarrays (CGH)
5) next generation sequencing (NGS)
