Lecture 4: Genetics and Human Development Flashcards
adult testing
-predict info about health for the future
testing before birth
- embryo biopsy (IVF)
- fetal DNA in maternal blood
- fetal free DNA (CF)
- maternal blood triple test (blood sample)
- ultrasound
- chorionic villus sampling
- amniocentesis
embryo biopsy (IVF)
- superovulation under if medicine?
- wait to 8 cell stage (differentiated cell)
- whole genome sequencing
- taking out one cell does not disrupt the development of the embryo
fetal DNA in maternal blood
- fairly new
- some fetal cells get in maternal blood circulation
- male pregnancy easy to differentiate from mother
- cells can live happily in mother circulation for many yrs.
- making it unreliable
- not where we are heading today
fetal free DNA (CF)
- fetus DNA not bound
- disappears after pregnancy
- mother gives up 10ml of blood around 7 weeks in pregnancy
- alot safer than amniocentesis
3-13%
- can be used to figure out if a child may have down syndrome
- use markers on the chromosome and do multiplex sequencing
- revolution prenatal testing
- only cost $600 in Australia
maternal blood triple test (blood sample)
- test for three compounds to determine if something is wrong with the fetus
- testing has to fall within a range
- AFP-high concentration, if you have neural tube defect
- HCG and Osteriol
- likelihood of a trisome
- has been going on for a while
- estimate risk that a mother will have a child with a spinal defect of ?
- subjectivity in interpretation
ultrasound
- routine
- done 11-12 weeks routinely
- @ 20 weeks know the sex of the fetus
- look a nuchal transluecency (gap measurement at the back of the neck)
chorionic villus sampling
- chorion is a membrane derived from the same tissue as the embryo
- separate maternal and fetal issue (contamination problem)
- 10-30mg chorion required
- done between 10 and 12 weeks of pregnancy
- older mothers (women in their 40 go right into sampling)
- same genetic origin as the fetus itself
- transdominal sampling of the chorion
- suck out member for karyote and fetus
- pick up chromosome
- keep for short or long term depending on what you are looking for in the pregnancy
Amniocentesis
- 10-12 weeks
- any earlier leads to effect in limb formation
- see if indicator of neural tube defect
- average in Australia is 16 weeks
- pull about 20 ml
- decreasing due to using the cell free technique
age and risk of aneuploidy in liveborn children
- aneuploidy is +/- a chromosome
- risk of aneuploidy increases with age
- 37 high risk age for significant testing
- exponential increase of down syndrome at age 37
women in population deciding to have children much later
- 29.3 median age of women
- median age of first time mother is continuously increasing significantly (6 more years added to the average age of mothers in 1986)
- 31.5 in Victoria
transmission of rates: aneupolidy happens
-nondisjuntion at anaphase 1-three copies
-nondisjunction at anaphase 2- three copies or 1
chromosome 13-gene poor, few genes ?
chromsome 18-low setties
-quite severe mental impairment
-either die really early after birth or miscarriage
trisome 21-level in old age occurs in 1/61
X chromosome not disjoining
Anaphase 1 or 2-Kleinfelters (XXY)
XXO
- normal phenotype
- reproduction problems
- disrupted miotic
XO-turner syndrome
aneupolidy occurs in older women
- coding of gene disrupted then the chromosomes don’t
- length of expendid miosis
complicated type of inheritance
- might find mutation in gene
- effect in one person may be entirely different in another person
pedigree way of demonstrating inheritance
- first thing that occurs in genetic testing
- pick up patterns of inheritance consanguinity-recessive traits come out of nowhere
- double line mating between couple with a common ancestor
X linked dominant or recessive
- higher proportionate of males that has an effect
- pedigree analysis critical for genetic inheritance doctore
X linked dominant
-if father carries trait, then all his daughters will have the trait
skipping a generation does not prove that the trait is recessive
dominant autosomal trait there but not everyone expresses it
lethality
ex. Achondroplasia
- interrupts the development of the limbs
- heterozygous dominant
- 1 in 4 pregnancies will terminate
variable expression
- same genotype, express differently
- more serious phenotype then other
- NF1
reduce penetrance
- has the same genotype but not expressing it
- ex. 6 or 7 finger
CF
- over 2000 mutations
- 127 of them result in defective protein
- deletion of phenylalanine-common
- ethic origin determines likelihood of mutation that will lead to CF
Fragile X
- can expand
- 3 base repeating
- hunting in the coding
- large testis
- stop expression of MMR gene
- Huntington disease
- produce toxic protein that cause defect
- degeneration of the brain
- loose control of movement
Number of repeated sequence
- determines if the disease is penetrance or not
- if inherited through father, it expands further and has a quicker effect
anticipation
-go through family pedigree, disease gets worse
heterogeneity
- 120 independent genes influence deafness
- same phenotype, but different genes (x-linked or autosomal)
- different genes contributing to breast cancer
genes influenced by environment
ex. neural tube defects, schizophrenia
- multifactorial
- threshold
- spinobiphida
- things you can and can’t control
multifactorial
-strong genetic component but also influence by the environment
threshold
- accumulate some of each
- different for men and women
- show phenotype or not
spinobiphida
- what causes it to increase in the environment
- take folic acid in the beginning of pregnancy to reduce risk
things you can and can’t control
- can’t control age, sex, genes from mom and dad
- can control environmental influence (like smoking for heart attack)
- only if we knew the environmental factors for cancer like breast caner
genomic imprinting
- gene only express from either paternal or maternal
- chromosome 15
- some genes only inherited from copy of mom or from dad
chromosome 15
- paternal
- obesity syndrome
- reduce testis
- maternal
- angelmann region
mitochondrial genome
- all mom
- have own genome in mitochondria
- male mitochondria disintegrates
- own genome and sequence
- 6,000 bases
- genes associated with energy and metabolism
- 100 mutations can result in phenotypic outcome
- nucleus is 1/56 to grandmother
- son will not pass mitochondria to offspring
