Genetics
see family history
see pregnancy screening
You inherit 50% of each parents DNA normally
half of each 50% you will share with your siblings i.e. 50% total
genotype: what genes are inherited
(haplotype: what group of genes were inherited together)
Phenotype: what genes were expressed
Euploid = complete sets of chromosomes i.e. haploid (23), diploid (46), triploid (69)...
Aneuploid = incomplete sets e.g. trisomy 21 is diploid +1
Mosaicism: more than one genotype present in an individual, with all cells originating from one zygote
Unrelated: 2-3% risk of birth defect
First cousins have 5% risk of birth defect
1st degree relative = share 50% DNA i.e. parent-child, siblings (identical twins are 100%)
2nd degree = 25% = half-siblings, grandparents, aunts/uncles
3rd degree = 12.5% = cousins
Anticipation: symptoms present earlier in subsequent generations
Imprinting: predictable silencing of a gene. i.e. maternal copy always express, or paternal always expressed
Non-paternity
Non-penetrance: a gene that usually is expressed is not (e.g. unexpected silence)
X-linked inheritance (generally only males affected, skipping generations through females, cannot be father to son)
- Dom (can have male sparing e.g. X-linked epilepsy and cognitive impairment)
- Rec
AD - (many affected, any sex)
AR - (few affected, any sex) (generally more severe, less variable, less likely new mutation cw AD)
Y-linked (only father to son)
Mitochondrial (only mother to child)
Genome = all nuclear and mitochondrial chromosomes
RNA splicing: exons remain after intron spliced
the exons together are called exome
Transcription: DNA to RNA
Translation: RNA to protein
Deletion: frame shift,
Duplication
Missense mutation: causes wrong amino acid to be inserted into protein
Nonsense mutation: causes stop codon and truncation of protein
Splice site mutation
X-inactivation: during blastocyst stage each cell independently inactivated an X chromosome. Hence variability between cells.
Expansion of triplet repeats in subsequent generation cause more severe disease
Robertsonian translocation (increase probs with their offspring but most normal, associated with many cancers)
Monogenic: single gene involved
Oligo: a few
Poly: many (most likely to inherit if affected parent was in a low risk group e.g. mother when male predominance)
Biostatistics
2 alleles, p and q
p + q =1, as you have one or the other
chance of homozygous p = p²
change of heterozygous = pq
chance of homozygous q = q²
Hardy-Weinberg equation: p²+ 2pq+ q² = 1, as you have one or another combination of alleles
p² is a high number, 2pq is low and q² close to zero
prev of AR disease = x = chances of getting it = (pq^2), /4 ( chances of homology parent are negl)
carrier = (prev x 4) sqrooted OR (sqroot of prev) x 2
Chorionic villus sampling
FISH
CGH array pick up copy number changes ie deletions and duplications
Heredity (see wiki)
Karyotype: will see monosomy, trisomy, translocation but not micro deletions
AR
Variable
DNA condensation
see pregnancy screening
You inherit 50% of each parents DNA normally
half of each 50% you will share with your siblings i.e. 50% total
genotype: what genes are inherited
(haplotype: what group of genes were inherited together)
Phenotype: what genes were expressed
Euploid = complete sets of chromosomes i.e. haploid (23), diploid (46), triploid (69)...
Aneuploid = incomplete sets e.g. trisomy 21 is diploid +1
Mosaicism: more than one genotype present in an individual, with all cells originating from one zygote
- Gonadal
- Somatic
Unrelated: 2-3% risk of birth defect
First cousins have 5% risk of birth defect
1st degree relative = share 50% DNA i.e. parent-child, siblings (identical twins are 100%)
2nd degree = 25% = half-siblings, grandparents, aunts/uncles
3rd degree = 12.5% = cousins
Anticipation: symptoms present earlier in subsequent generations
Imprinting: predictable silencing of a gene. i.e. maternal copy always express, or paternal always expressed
Non-paternity
Non-penetrance: a gene that usually is expressed is not (e.g. unexpected silence)
X-linked inheritance (generally only males affected, skipping generations through females, cannot be father to son)
- Dom (can have male sparing e.g. X-linked epilepsy and cognitive impairment)
- Rec
AD - (many affected, any sex)
AR - (few affected, any sex) (generally more severe, less variable, less likely new mutation cw AD)
Y-linked (only father to son)
Mitochondrial (only mother to child)
Genome = all nuclear and mitochondrial chromosomes
RNA splicing: exons remain after intron spliced
the exons together are called exome
Transcription: DNA to RNA
Translation: RNA to protein
Deletion: frame shift,
Duplication
Missense mutation: causes wrong amino acid to be inserted into protein
Nonsense mutation: causes stop codon and truncation of protein
Splice site mutation
X-inactivation: during blastocyst stage each cell independently inactivated an X chromosome. Hence variability between cells.
Expansion of triplet repeats in subsequent generation cause more severe disease
Robertsonian translocation (increase probs with their offspring but most normal, associated with many cancers)
Monogenic: single gene involved
Oligo: a few
Poly: many (most likely to inherit if affected parent was in a low risk group e.g. mother when male predominance)
Biostatistics
2 alleles, p and q
p + q =1, as you have one or the other
chance of homozygous p = p²
change of heterozygous = pq
chance of homozygous q = q²
Hardy-Weinberg equation: p²+ 2pq+ q² = 1, as you have one or another combination of alleles
p² is a high number, 2pq is low and q² close to zero
prev of AR disease = x = chances of getting it = (pq^2), /4 ( chances of homology parent are negl)
carrier = (prev x 4) sqrooted OR (sqroot of prev) x 2
Chorionic villus sampling
FISH
CGH array pick up copy number changes ie deletions and duplications
Heredity (see wiki)
Karyotype: will see monosomy, trisomy, translocation but not micro deletions
- Turners syndrome (45 X)
- Down syndrome (47,XX/Y,+21) 1:1,100
- Edwards syndrome (47, XX/Y, +18)
- Patau syndrome (47, XX/Y, +13)
- Kleinfelter syndrome (47, XXY)
AR
- Tay–Sachs disease (neurodegenerative)
- Sickle-cell disease
- Cystic fibrosis
- PKU
- Duchenne muscular dystrophy deletion (1:3,600 boys)
- Haemophilia A and B (1:7,000 boys)
- Fragile X (dominant with X inactivation so females not affected) triplet repeats, autism, Int Impairment
Variable
- Thalassemias
DNA condensation