Development & genetic diseases Flashcards
genome mutation
loss or gain of entire chromosome
rare but lethal
chromosomal mutation
alteration in one or more chromosomes, can be identified by karyotyping
gene mutation -partial or complete
partial- mutation of one of the nucleotide bases. Complete- deletion of gene from chromosome
Overall effects seen from single gene mutation
can alter structure/function of nonenzymatic protein.
can alter plasma membrane, affecting transport
can result in enzyme defect
can cause unusual reaction to medication
Classes of DNA mutation
-Point mutation >>silent mutation >>missense mutation >>nonsense mutation -frameshift mutation -trinucleotide repeat disorders
Point mutation
change in a single nucleotide in a gene. Can be 3 different types of point mutations– silent, missense, and nonsense.
Silent mutation
where mutation codes for same amino acid. This means there is not phenotypic effect/CS&S.
Missense mutation
where mutation codes for different amino acid. more likely to cause phenotypic effect/CS&S.
EX: sickle cell anemia
sickle cell anemia
where adenine is replaces thymine, which causes valine to be expressed in transcription. This causes beta globin chain deformation, which causes shape deformation. Shape deformation leads to loss of lumen when sickle cells buildup and cause an occlusion in BV
Nonsense mutation
mutation codes for premature termination of protein synthesis. Will have phenotypic effect/ CS&S. EX. beta-thalassemia.
Beta thalassemia
No synthesis of hemoglobin a. RBCs are smaller in size, decreased ability to carry oxygen–> anemia
Frameshift mutation
insertion/deletion of nucleotides. This shifts reading frame for DNA, which can cause coding for different proteins. Ex. Tay-Sachs disease
Tay-Sachs
frameshift mutation on chromosome 15.
Autosomal recessive inheritance.
more prevalent in European descent.
Body lacks hexosaminidase A which breaks down gangliosides —lipids in neurons
Tay-Sachs CS&S
progressive neurologic degeneration:
Cherry red spot in eye!, deafness, dementia, decreased motor tone, paralysis, seizures/epilepsy
Appears at 3-6 months of age, child dies around 4-5. Palliative treatment only
Trinucleotide repeat disorders
errors in DNA replication due to amplification three nucleotides. increases 10 fold each generation, CS&S may not show in first or second, and become more severe with every generation–> associated with ANTICIPATION
Ex. Huntingtons disease and Fragile X
Fragile X
Sex linked (X) disorder, trinucleotide repeat disorder. CS&S= anxiety, hyperactive, ADD, 1/3rd autistic/-like. sometimes seizures. Long narrow face, large ears, prominent jaw& forehead, flexible fingers, macroorchidism after puberty. Normally FMR1 helps with synapse formation and shuttles mRNA and is CGG repeated 10-40 times. when mutated, CGG repeats 200+ times and S&S seen
Down syndrome
Autosome disorder, extra copy of chromosome 21. most common chromosomal disorder. Chances of getting DS increases with age of mother, 1:25 births if over age of 45. CS&S- flat face, epicanthic folds, macroglossia, simian crease, cardiac malformation, ^susceptibilty to infection, ^ risk of leukemias, alzheimer type dementia developed young. Amniocentesis detects with ^ beta hCG, and low alpha fetoprotein
Cause of Down Syndrome
95% due to maternal meiotic nondisjunction.
4%Robertsonian translocation, fusion of chromosome arms
1% due to mosaicism
Patau syndrome/ trisomy 13
results from nondisjunction during maternal meiosis. CS&S: congenital heart defects, eye defects, cleft lip/palate, holoprosencephaly, mental retardation, deafness. most die withing 2.5 days after birth
Cytogenic disorders of sex chromosomes
Turner syndrome, Klinefelters syndrome
Turner’s syndrome
sex chromosome disorder in females involving 2nd X chromosome- can either be altered/missing- also called monosomy X. the cause of TS is spontaneous nondisjunction in 60% and mosaicism in 40%.
correlated with missing one SHOX gene -since one on each chromosome, which is protein that helps development of skeletal system –> short, malformed limbs
Turner’s syndrome CS&S
short stature/ limbs, loss of OVARIAN FUNCTION, webbed neck, low hairline, wide set nipples, shield like chest, short fingers, moles.
lymphedema of hands and feet in infancy, 1/3rd born w/ heart defects, NORMAL intelligence
Klinefelter’s syndrome
sex chromosome disorder in males w/ extra X chromosome added. Hypogonadism in males.
Caused by nondisjunction. Decreased levels of testosterone because inhibin causes a sequence of events that eventually turns it into estradiol, which gives feminine appearance. Small testis, gynecomastia, dec. facial/body hair, infertile, tall stature, learning disabilities-speech/language. ^ chance of breast cancer/lupus.
Genetic disorders: Mendelian pattern of inheritance
Autosomal dominant, autosomal recessive, and sex linked
