Genetics 2 Flashcards
Describe dominant autosomal disorders with example
single gene disease multiple egenerations affected child of affected person = 1/2 chance m+f equally likely to be effecting vertical degree pattern gain of function-gene makes protein with a new function
huntingtons- proteins aggregate
Describe autosomal recessive disorders with example
two copies of non working gene loss of function mutations- sibling of affected child has 1/4 chance of being affected m+f equally effected horizontal pedigree pattern
cystic fibrosis- chloride channel is defective
Why in brittle bones does a mutation in collagen affect skeletal abnormalities
Skeleton initially laid down ad collagen, is mineralised later
if collagen is defective then bones are
Describe X linked recessive and dominant disorders
RECESSIVE- mainly affects males
brothers of affected son have 1/2 risk, sisters 1/2 risk of being a carrier
affected father= all sons will be healthy, all daughters carriers
carrier mother= 1/2 carrier daughter, 1/2 affected son
e.g haemophilia
DOMINANT-
affected father= all daughters and non sons affected
Affected mother= 1/2 chance son or daughter
Describe Y linked disorders
only males affected
all sons of affected father
vertical degree mater
Describe mitochondria disorders and the variability in them
Have their own DNA and all mitochondria maternally inherited
all children of affected woman are affected
variability as mitochondria replicate via binary fission so can lose or gain mutated genes due to random segregation , will only express the disease phenotype if over a threshold. can change with time and develop with age
In brittle bones what protein changes and how does this affect electrophoresis
From glycine to cysteine. Cysteine can from disulphide bridges to link chains together, 2-mercaptoethanol breaks these.
Glycine is more negative than cysteine so in electrophoresis one of the chains will move less than normal collagen chains.
How does the protein change in brittle bones change the assembly of type 1 collagen
glycine changes to cysteine, and cysteine can’t fit so fibrils will be affected.
even if only half colA1 protein is mutated all fibrils will be affected when they are packed together
If the patients are genetically identical what is the likely cause of variance in phenotype?
environment
Prenatal diagnostic tests for brittle bones/ osteogenesis imperfect
Sample from foetus: amniocentesis, chronic villus sampling
RFLP- mutation makes or breaks restriction site, gel electrophoresis
or
PCR- amplify, gel then probe for mutation
If the patients are related but NOT genetically identical what is the likely cause of variance?
Effect of other genes which interact with the disease
could be environment
If the patients are unrelated but the same mutation what is the likely cause of variance?
unstable mutations- change with time/age
different mutations in the same gene
What do the dark and light bands of karyotyped chromosomes mean
Bands have different staining, dark (heterochromatin) are more compact and have fewer genes, light 9euchromatin) are more open and have more genes
Describe basic nomenclature
p= short arm q=long arm del- deletion der- derivative (extra material dup ins \+/- BEFORE chromosome number is gain or loss of whole chromosome \+/- AFTER chromosome number is gain/loss of part of chromosome
normally put total number of chromosomes then where the gain or loss is
What is aneuploidy and how does it happen
Abnormal number of chromosomes: non disjunction
In normal meiosis the aim is to reduce from diploid 2n=46 to haploid n=23, allows genetic variation through random assortment and recombination
Non disjunction results in an uneven number of chromosomes In daughter cells if in Meiosis I all daughter cells affected, if meiosis 2 then half but it still results in a trisomy and monosomy
Why is sex chromosome aneuploidy tolerated
there is X inactivation of excess X chromosomes, only one is active
low gene content of Y chromosome
both X and Y have PAR (pseudo autosomal region) - regions of a chromosome that remain active even after inactivation
Where does trisomy 21 arise and what are the risk factors
in maternal non disjunction- the risk of this increases with age because the oocyte remains in meiosis 1 for a long time and the factors which hold chromatids together are degraded
Primary spermatocytes undergo many divisions per year and can accumulate defects.
paternal age doesn’t affect, only for some single gene disorders that enhance sperm viability
Paternal smoking is a risk factor
What is crossing over, when does it occur and how an it go wrong/lead to aneuploidy
In prophase 1, increases genetic diversity
pair of chromosomes aligns, chiasma forms and crossover occurs
If the chromosomes misalign then they can cross over wrongly leading to del - deletion of a gene in some and dup- duplication of a DNA region in others
What is chromosome inversion and what are the types
Paracentric - far from centromere
Pericentric- around centromere
people often unaffected, happens when the DNA that breaks off gets inverted
What is translocation and insertion
involve non homologous chromosomes
In an insertion, DNA from one chromosome is moved to a non-homologous chromosome in a unidirectional manner. In a translocation, the transfer of chromosomal segments is bidirectional and reciprocal – a reciprocal translocation.
What is Williams syndrome, what is the phenotype and how can it be detected
A deletion from one chromosome, will have short upturned nose, long philtre, arched eyebrows, friendly+ social cocktail party personality
7q11.23del
FISH (fluorescent thing) will detect a lack of elastin on effected chromosome
if its a 7q11.23 duplication then will be the opposite- delayed speech, autistic behaviours, flat eyebrows, broad nose
What are the three classes of chromosomes
Metacentric- has a short arm (p) and a long arm (q)
Submetacentric- short arm becomes shorter
Acrocentric- short arm replaced with a stalk and small bit of DNA
What is Robertsonian translocation
between Afrocentric chromosomes, homologous or non homologous
most show no effects but problems in offspring
13+14, 14+15, 14+21
What is mosaicism
Presence of two or more populations of cells with different genotypes
X inactivation leads to mosaic expression
Mosaicism can arise via: non disjunction or loss of extra chromosome: causes milder phenotype and some aneuploidy can survive if mosaic
What is the mendelian trait
controlled by a single gene, phenotype follows dominant e.g. ABO blood group
What is a complex trait
Controlled by multiple genes and the effect of the environment e.g height, weight, skin, eye colour
What are some examples of Complex and mendelian diseases
mendelian- cystic fibrosis, sickle cell anaemia
complex- diabetes, cardiovascular disease, asthma, mental health diseases
What are SNPs, how can they be used and why are they useful
Single Nucleotide Polymorphisms
they are DNA sequence variations that occur when a single nucleotide is changed, the single nucleotide polymorphism frequency between control groups ad ones with disease are found, if one is more frequent its likely to be a susceptibility gene
They are useful for public health, can target those who have susceptibility genes- high risk groups and have preventative strategies from the beginning which will save resources in the long term.
What is missing heritability and what could be the reason for it
genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values.
could be due to :
rare variants of small effect, low frequency variants with intermediate effects, interactions between susceptibility genes, miscalculation of heritability
What is pharmacogenetics and why is personalised medicine a thing
The study of variability in drug response due to genetic difference, it may have no effect on some and a severe effect on others
The action of the drug is the same bu the response and how its metabolised is genetic
aims for increased efficacy and decreased adverse side effects
personalised medicine aims to treat patients depending on specific characteristic of their disease
What prenatal scans are there and why are they useful
Nuchal scan- 10-14 weeks gestation- dates pregnancy, diagnoses multiple pregnancy, major fatal abnormalities, early miscarriage or risk of Down syndrome and other chromosomal abnormalities by looking at maternal age, blood hormone levels, nuchal translucency thickness, blood flow through metal heart
Midtrimester anomoly scan
Ultrasound scans
What is nuchal translucency and what does it indicate
Thickness of fluid at back of neck higher than 3mm can indicate: 1) chromosomal abnormalities like downs 2) birth defects- cardiac anomalies, pulmonary defects, renal defects, abdominal wall defects 3) skeletal dysplasias
NT is a screening test and is not diagnostic
When is prenatal testing arranged and with what aim
Following abnormal nuchal or mid trimester scan
inc risk of downs
if previous pregnancy affected
if parents carrier of chromosome rearrangement or genetic condition
to inform and prepare parents, allow in utero treatment, manage remainder of pregnancy, prepared for complications after, allow termination of an affected foetus
