DNA and Inheritance Flashcards
what are van der waals forces
weak interactions between atoms and molecules following fluctuations in electrical charges, these are only relevant when the 2 molecular surfaces fit closely together
what are proenzymes
they’re enzymes that have to be cleaved to be activated
what do you call an enzyme that forms a covalent bond and is regenerates and the end of the reaction
an action transfer coenzyme
what is an autosome
a chromosome other than the sex chromosomes that occurs in pairs in a diploid cell
define homozygous and what causes a greater degree of homozygosity
the allele at a partticular locus for a particular gene, along a chromosome that is identical on both sister chromatids. If the parts share a common ancestor, so are consanguinous
polymorphism
frequent heredity variations along a particular locus that must occur in more than 1% of the population
what is a recessive allele?
it is one that manifests only in the homozygote
assortative mating
a form of sexual selection in which individuals with similar phenotypes mate with eachother more than would be expected under a random mating pattern
what 3 things can a phenotype be?
physical, biochemical and physiological
a position of a gene on the genetic map is…
locus
hemizygous. In what 2 situations does this manifest
this is where you posses only one allele, so refers to only one locus on one chromosome that doesn’t exist on the other. as with x-linked genes in a MALE or when one copy of a gene was deleted
what does a coat hanger with a line through it mean on a inheritance tree?
twins that are non-identical. so a lack of a line would indicate them are identical.
what are 4 reasons to have a phenotype of an autosomal dominant condition when it is absent in the parents
a new mutation, anticipation of gonadal moscaisism, penetration
define anticipation
whereby a disease affects a generation more severely or earlier on due to expansions in triple repeats in the DNA. The hairpin loop grows and it has a tendency to expand through generations
if the affected individuals are in many generations and of both genders, what is the likely pattern of inheritance?
autosomal dominant
what is penetrance?
the percentage of individuals with a specific genotype that show the expected symptoms
expressivity
this refers to a range of symptoms/ phenotypes that result fro the same specific genotype
when is variable expression the likely explanation for certain symptoms
on seeing a family where the disease’s features are in all of the generations but with more severe symptoms. usually caused by a combination of genetic and environmental factors
what type of feature in an inheritance tree will allow you to distinguish between autosomal dominant and recessive diseases?
In both cases, several generations are affected, but with autosomal recessive, typically only one generation is affected rather than several
what is consanguinunity
a reproductive union between 2 parents
autozygosity
the genes of a homozygote that are identical copies of the ancestral gene because the parents were consanguinists. so homozygosity by descent, so inheritance of the identical alleles from parents that were from the same family
if someone is tested and they test negative for being a carrier of cystic fibrosis, what is the % that they are still carriers and why
10% because the genetic test only detects 90% of the gene causes of cystic fibrosis. so as the % carreir frequency in the population is 1 in 25, then it’s 1 in 250 (10% of 25)
what enzyme are you deficient in if you have cystic fibrosis and where is it produced?
trypsinogen. the pancreas
if a person has a sister with cystic fibrosis but none of the parents are sufferers, what is the % that this lady is a carrier of the gene
a half. as her parents must both be carriers and there is a 50% chance that she inherited the faulty gene from a parent
in general, what is the percentage that a child will be a sufferer of an autosomal recessive disease if both parents are carriers?
a quarter
how many genes do you share with your siblings?
a half
what sex of child is definitely a carrier of a sexlinked condition that a father has?
females
what is lyonization?
an imprint put onto a certain DNA sequence. it involves x chromosome inactivation, leading to only one of the x chromosomes in a female cell being active
what is the name given to the sign displayed by people in muscular dystrophy where they have proximal limb weakness and have to use their hands to crawl or walk up their body. so due to a lack of hip and thigh muscle strength
Gower’s sign
if the mother is affected by an x-linked condition, what is the percentage of her having an affected son?
100%
define imprinting
where only one allele of a gene in the heterozygote is activated, so can be either from the mother or from the father, for example mitochondrial disease, is imprinted from the mother, in the egg
what is thought to be the main influencing method on DNA that causes imprinting
methylation
in what type of non-mendelian inheritance is the likelyhood of having a child with a certain disease increased by having had a child already that suffers the disease?
multifactorial
what gene is associated with a. breast cancer b. ovarian cancer
a.BRCA2 b.BRCA1
if penetrance is 80% and the chance of developing cancer if you have a mutation in the BRCA gene is 50%, what is the chance of actually developing cancer? (this is all because it is a multifactorial condition
80x50= 4000, /100=40%
give 4 criteria to conclude that a condition is multifactorial
- the risk of aquiring the disease is higher in the relatives of the affected compared to the general population
- the risk directly varies with the degree of the genetic relationship with the relatives and then rapidly decreses in risk as the relationship becomes more distant
- the risk varies with the severity of the affected relatives
- the risk varies with the no. of the relatives affected
define concordance rate
the percentage of twin pair studies that both have the condition
if the concordance rate is high for a particular disease would you expect it to be a condition that is more dependent on genetics or the environment?
genetics
define heritability
this is the degree to which a disease can be caused by genetics as opposed to the environment (as applied to multifactorial condition)
if the heritability of a disease is 80%, what percentage of cases are due to the environment?
20%
what type of twin study do you need to reliably use the concordance rate to calculate heritability?
monozygotic twin studies
If there is a multifactorial condition in which females are usually the more affected sex, is the risk higher to relatives of the family if the girl is affected or if the boy is the one affected
the relatives if the boy is affected. so you have increased the genetic component of the condition by the boy having the disease first (ie the first person to suffer the disease being of the usually less affected population).
what does a statistic for the liability of an individual to a particular disease combine?
genetic and environmental risks into a single entity.
which way is the curve for liability shifted for the relatives of an affected individual compared to the general population. and how does increasing the relationship to the relative affect this?
to the right. the greater the relationship the greater the shift
beyond the threshold for the liability curve, what is represented a.for the general population b. for the relatives of the affected
a. population incidence of the disease
b. Familial incidence
what does being beyond the threshold of the liability curve indicate
that in your lifetime you will get the condition
what is on the a. x axis of a liability curve b. y axis of a liability curve
a. liability b. number of people
define polymorphism
where a gene product is made but it is less efficient than the one made without a mutation
what is a SNP? (think polymorphism)
single nucleotide polymorphism
what is the likely reason that a child is a sufferer of an autosomal dominant condition and genetic tests have PROVEN that the parents do not carry the gene (so can’t be anticipation). give 2
gonadal moscaisism or non-paternity
define somatic moscaisism
whereby a mutation may have occurred not in meiosis but in mitosis at a very early stage of the parent’s development. Eg in cell no. 8. So, the tissues of the parent then consisted of greater than one cell line due to this error in mitosis after conception. This mutation then happened to be in the parent’s germline or gonadal tissue and so was passed onto the offspring.
define gonadal moscaisism
whereby the genetic mutation is present in the gonadal tissue only, so is not in the somatic tissue of the parent. This is due to a mutation that occurred in the formation of the gametes during meiosis
define chorea
random purposeless movements
what is the extra chromosome that causes down syndrome?
chromosome 21, so trimosy
what is the main reason why some people that inherit an extra chromosome survive but others do not
It depends on the size of the extra chromosome, the smaller it is, the less extra genes that are inherited and the more likely they are to survive
define aneuploidy
the presence of an abnormal number of chromosomes, eg 45 or 47, so extra or less
define genomic conditions
ones that arise from direct changes to the human genome rather than base changes along a particular chromosome
when is swapping of DNA between chromosomes a problem?
when it’s unbalanced
define a mis-sense mutation
a single base change that changes the codon and so leads to replacement of one of the amino acids in a protein with another that leads to a different protein being made
what type of mutation does not result in alteration to the final polypeptide?
a mutation in the promotor sequence for a gene, so alters the expression of that gene
what is a non-sense mutation
an alteration to the base sequence of the DNA that results in a stop codon being coded for. so, the RNA prematurely detaches from the ribosome and a truncated protein is made. An inframe deletion means that the stop codon can only be created at the site of the alteration whereas an out of frame deletion may result in a stop codon being coded for further along the DNA
Define non-sense mediated decay
whereby the non-sense mutation will result in a protein that is unable to perform its function and so the mRNA coding for it is broken down
what type of deletion mutation affects the final protein more?
out of frame deletion, so where the base deletions don’t occur in a multiple of 3, so the reading frame is changed
give 4 criteria to conclude that a mutation is pathogenic rather than a polymorphism
- it results in the change in the amino acid sequence
- it is not seen in normal people, Ie. people not showing symptoms
- it results in a change in the splice site of the gene
- it affects protein function, either its regulation or the actual function of the final protein
what are three methods of dominance
loss of function, gain of function and dominant negative mutations
what is a gain in function mutation? what can cause it?
an increase in the gene dosage, so too much protein is made. The recognition site for the degradation of that protein has a mutation and so the protein is not broken down an it accumulates
what is a dominant negative mutation
whereby in the heterozygous sate, the protein from the mutatant allele interferes with the protein from the normal allele. so the mutated allele works antagonistically to the normal, wild type allele
if a normally recessive gene undergoes dominant negative mutation, what percentage of the offspring will be normal
only 25% instead of 75%. so i looks like a dominant or semi-dominant phenotype.
define allelic heterogeneity
different mutations at the same locus of different chromosomes causes the condition. this is what leads to such variable symptoms in cystic fibrosis. eg someone has fertility problems and someone else can’t breathe
locus heterogeneity
a condition caused by mutations in genes of different chromosomal loci
give 3 types of genetic test that are used in clinic
carrier, predictvie and diagnostic
what is a criterion that must be met to do a diagnostic genetic test
the person already has symptoms, so the mutation test will confirm the diagnosis
predictive testing involves testing…
health at risk family members (the mutation in the family is usually dominant)
what type of inheritance pattern is usually involved in carrier testing? and when is it usually performed?
autosomal recessive and X-linked disorders. In a couple who want to have children
what are the 2 types of pre-natal tests
chorionic villus sample (CNS) or amniocentesis
what tissue is taken in a chorionic villus sample(CNS)? and in an amniocentesis?
part of the placenta, fluid around the baby containing skin cells
what type of genetic testing targets the population as a whole rather than individuals
genetic screening, so not just high risk families
what does a susceptibility test determine?
an increased or decreased RISK for a mutifactorial condition
