Genetic Abnormalities Flashcards
what are the classifications of mutations?
- scale
- loci
- type of cell they occur in
what determines if a mutation is germline or somatic?
the location
if a cell with a germline mutation is fertilised, how many cells in that person will be affected?
all nucleated somatic, 50% of its gametes
what is the difference between somatic and germline mutations?
somatic cant be passed
germline is hereditary
what is the worst consequence of mutation?
cancer - usually takes 2 mutations
what happens if a somatic cell is mutated?
only progeny of that cell carry the mutation
what is the difference between Chromosome and gene mutations?
chromosome - big scale (entire or large section)
missing or gain of chromosomes
large scale rearrangement
Gene mutations- Small scale, Single gene A lot are silent – doesn’t change Alter protein product/ protein product with altered function Coding sequence = function change Regulating = protein product Not loss of function, just change
what is the significance of Oncogene mutations?
regulate cell growth – growth in cell function.
what 4 ways can you identify a genetic cause?
Family studies
Chromosome abnormalities
Molecular characterisation
Association of an allele with a disease
How can you use family studies to identify a genetic cause?
Family tree - Identify affected/ carriers. Recessive – carriers
Twin studies. Measure how identical/non identical compare to developing the disease. Strong for genetics BUT shared env….. split up identical twins
How are chromosome abnormalities used to identify a genetic cause?
Chromosomes condensed and visible mitosis/meiosis
Variation in: chromosome number, length, banding patterns
How is Molecular characterisation used to identify a genetic cause?
DNA sequence
Analysis of gene expression –measurement of mRNA level
Measurement of protein function
Protein level
what is Familial hypercholesterolaemia?
Affected individuals can not remove LDL from blood due to lack of functional receptors on surface of cells
how many classes of Familial hypercholesterolaemia are there?
4
what is type 1 Familial hypercholesterolaemia?
No receptor produced due to deletion of large section of gene
what is type 3 Familial hypercholesterolaemia?
Single base change in gene receptor protein that can not bind LDL
what is type 4 Familial hypercholesterolaemia?
Single base change in gene receptor protein that binds LDL, but can not be taken up by endocytosis
what is type 2 Familial hypercholesterolaemia?
Normal receptor produced, but protein broken down before it reaches cell surface
Due to defective post-translational processing of receptor
Results from lack of activity of enzyme involved in processing
How is type 2 diabetes associated with gene inheritance?
Cause = tissue resistance to insulin Strong involvement of genetic factors first degree relative – big risk. Avoid by exercise etc but still risk need to pin down the genes different families –different genes
how is peak bone mass associated with Interaction of Genetic Factors with Other Determinants?
peak bone mass – osteoporosis in later life risk
max bone mass (20-30 yrs)
determines susceptibility of osteoporosis (bone mass below a certain value)
doesn’t effect rate of loss but more to lose depending on the mass
influenced by genetic and hormonal (80%) , diet exercise (20%)
how does diabetes type 1 have inherited susceptibility?
HLA system (DR3/4) protein – genotypes that 95% have
Have those proteins – less ability to distinguish between self and non self
Genotypes associated with an increase in likelihood of developing autoimmunity
what is type 1 diabetes?
cause = loss of insulin production
autoimmune destruction of pancreatic B cells
what is the risk of type 1 diabetes between twins?
only 40% change both identical twins affected = not strong genetic factor
what genotypes are associated with type 1 diabetes?
95% of affected individuals have HLA-DR3 or HLA-DR4 genotypes compared with 45% of general population
how do you acquire type 1 diabetes?
Virus or other environmental agent -> Immune response -> Autoimmune destruction of B cells in susceptible individuals
what is Deaf1 and what does it do?
deformed epidermal auto regulatory factor 1
it is a protein that controls production of molecules needed to eliminate immune cells that destroy pancreatic B cells
what is the significance of shorter variant form of Deaf1?
prevents full-length form from functioning properly
the Level of shorter variant form is higher in type 1 diabetes than healthy people
how many conceptions are spontaneously aborted?
15-20%
how many spontaneous abortions have chromosomal aberration?
30%
how many chromosomal anomalies cause termination before birth?
90%
what is non-disjunction??
chromosomes fail to separate appropriately during meiosis or mitosis
results = 1 daughter cell too many, one too few
what is polyploidy?
presence of >2 multiples of haploid chromosomal cell – (somatic has 2x haploid, can have 3x)
incompatible with survival in humans
whole set the wrong way
what is aneuploidy?
not exact multiple of the haploid set
single chromosomes move the wrong way
accounts for high proportion of chromosome aberrations
many forms incompatible with humans
what is monosomy?
Loss of 1 chromsome
complement = 2n-1
2n expected in somatic cell
so loss of 1 chromosome = 2n-1
what is the complement of turner syndrome?
45,X
Missing chromosome of sex
Should be 45XY/XX
what happens if a complement is 45X?
female in terms of phenotype but ovaries and breasts underdeveloped
genitals there though
what is trisomy?
Gain of 1 chromosome
Complement = 2n+1
what is the complement of klinefelter syndrome?
47,XXY
what happens to people with klinefelter syndrome?
external male genitalia affected
cant reproduce – testes not developed
what are the characteristics of deletion?
loss of part of chromosome
breaks in chromosome or unequal crossing over in meiosis
may lower gene expression due to decrease in gene dosage
may cause problems during crossing over in meiosis
partial chromosome
what is Cri-du-chat syndrome and what is its complement?
46,5p-
loss of part of short arm of chromosome 5
P arm is the short arm
Chromosome 5 deletion. Short arm is deleted
larynx not developed properly
Cry of the cat – sound like a cat
what are the characteristics of duplication?
Part of chromosome present more than once in genome
Results from unequal crossing over in meiosis, or earlier replication errors
May gene expression due to in gene dosage
May cause problems during crossing over in meiosis
what are the characteristics of inversion?
Segment of chromosome turned round
Involves 2 breaks in chromosome inversion reinsertion of sequence
No loss of DNA
May alter expression of genes in inverted sequence (position effect)
May cause problems during crossing over in meiosis
what are the characteristics of translocation?
movement of part of a chromosome to a different chromosome
no loss of dna
position effect
may cause problems during crossing over in meiosis
50% gametes will contain one normal and one affected chromosome = duplication and deletion
some gametes will have normal and mutant/ 1 mutuant / 1 normal = short/long = AFFECTS THE WAY THEY PAIR
some get more/less
