T1 human genetics

nucleotide - composed of

sugars + phosphates + nitrogenous bases

types of nitrogenous bases

pyrimidines & purines

pyrimidines bases

cytosine, thymine, uracil

purines bases

guanine, adenine

DNA - what base

thymine

RNA - what base

uracil

central dogma

flow of genetic information from DNA → RNA → protein 

types of mutations

substitution (point mutation), insertion, deletion

types of point mutations

silent, nonsense, missense

silent mutation - outcome

same functional protein

silent mutation - changes

DNA & mRNA level

nonsense mutation - outcome

shorter protein

nonsense mutation - changes

codon for amino acid → stop codon

types of missense mutation

conservative & non-conservative

conservative mutation - changes

DNA level, mRNA level, protein level

conservative mutation - outcome

similar function protein

non-conservative mutation - changes

DNA level, mRNA level, protein level

non-conservative mutation - outcome

protein function change

genetic disorders - types of mutations

gene mutations & chromosome mutations

types of base substitutions

transition & transversion

transition mutation

purine → purine OR pyrimidine → pyrimidine

transversion mutation

purine → pyrimidine

frameshift mutations

insertions & deletions

insertion mutation - diseases

huntington’s disease & fragile X syndrome

huntington’s disease & fragile X syndrome - type of mutation

trinucleotide repeat expansion

huntington’s disease - inheritance pattern

autosomal dominant

huntington’s disease - genetic change

insertion of CAG to HTT gene → more repeats than normal

huntington’s disease - clinical features

affect body movement, loss control of emotions & ability to concentrate

fragile X syndrome - inheritance pattern

x-linked

fragile X syndrome - genetic change

expansion of CGG repeat to FMR1 gene on X chromosome 

deletion mutation - diseases 

cystic fibrosis

cystic fibrosis - inheritance pattern

autosomal recessive

cystic fibrosis - genetic change

deletion mutation in CFTR gene → removes phenylalanine from CFTR protein

cystic fibrosis - clinical features

thick sticky mucus that clogs lungs → infection

block pancreas → digestive enzymes cannot reach intestine

substitution mutation - diseases

sickle cell disease

sickle cell disease - inheritance pattern

autosomal recessive

sickle cell disease - genetic change

substitution on HBB gene on chromosome 11 → missense mutation

chromosome mutations - types

structural abnormalities & numerical chromosome abnormalities

chromosome mutations - structural abnormalities - disorders

cri du chat, williams syndrome, charcot-marie-tooth disease type 1A, four-ring syndrome, burkitt lymphoma 

cri du chat: the cat’s cry - mutation

deletion of part of short arm of chromosome 5

cri du chat: the cat’s cry - clinical features

wide eyes, small head & jaw, mental health problems

williams syndrome - mutation

deletion of part of chromosome 7

williams syndrome - clinical features

growth delay before and after birth, short stature

charcot-marier-tooth disease type 1A - mutation

duplication of gene coding for peripheral myelin protein 22 on chromosome 17

charcot-marier-tooth disease type 1A - clinical features

muscle weakness, decrease muscle size 

four-ring syndrome - mutation

portion of chromosome 4 is inversion

four-ring syndrome - clinical features

cleft palate, club feet

burkitt lymphom - mutation

chromosome translocation involving Myc gene

euploid cell

contains one complete set of chromosomes of exact multiples of full sets 

polyploid cell

contains multiple of the normal haploid number of 23

aneuploid cell

contains chromosome number that is not an exact multiple sets of the haploid set 

aneuploid cell - types

autosome aneuploidy & sex chromosome aneuploidy 

non-disjunction in meiosis I

homologous chromosomes don’t separate 

non-disjunction in meiosis I results in…

2 (n+1) & 2 (n-1)

non-disjunction in meiosis II

sister chromatids don’t separate 

non-disjunction in meiosis II results in…

1 (n+1), 1 (n-2), 2 (normal n)

chromosome mutations - numerical chromosome abnormalities

polyploidy - syndrome

triploid syndrome

triploid syndrome - genetic description

3 sets of chromosomes instead of 2 / 69 chromosomes instead of 46

autosome aneuploidy - syndromes

down’s, edward’s, patau’s

down’s syndrome - karyotype

trisomy 21 → 47,XY or 47,XX → +21

down’s syndrome - clinical features

short stature, broad hands, stubby fingers & toes, protruding tongue → speech difficult

edward’s syndrome - karyotype

trisomy 18 → 47,XY or 47,XX → +18

edward’s syndrome - clinical features

several abnormalities in child’s system, shorter lifespan than down’s syndrome

patau’s syndrome - karyotype

trisomy 13 → 47,XY or 47,XX → +13

patau’s syndrome - clinical features

several abnormalities in child’s system, shorter lifespan than down’s syndrome

sex chromosome aneuploidy - syndromes

klinefelter’s, jacobs, turner’s, triple X

klinefelter’s syndrome - karyotype 

47,XXY or 48,XXXY → males with extra X chromosome

klinefelter’s syndrome - clinical features

tall stature, small testicles, enlarged breasts

jacobs syndrome - karyotype

47,XYY → males with extra Y chromosome

jacobs syndrome - clinical features

tall & thin, aggressive, antisocial, behavioral patterns

turner’s syndrome - karyotype

45,XO → females with 1 X chromosome instead of 2

turner’s syndrome - clinical features

short stature, short broad neck, broad chest

triple X syndrome - karyotype

trisomy X → 47,XXX → females with extra X chromosome

triple X syndrome - clinical features

taller than average

X chromosome inactivation - how it works

each cell randomly choose 1 X chromosome (mom/dad) to inactivate → coat with XIST → DNA methylation → chromosome condense → barr body

X chromosome inactivation - chosen X chromosome becomes coated by 

XIST (special RNA)

X chromosome inactivation - XIST RNA triggers…

DNA methylation at CpG island 

X chromosome inactivation - chromosome condense to become…

barr body