Genetics SSN 2 Flashcards
oocytes formed as
fetus
female meiotic prophase at
14 weeks gestation
first meiotic division stops at ____, resumes/completes at ovulatoin
diplotene (when homologs repel)
meiosis II happens after
fertilization
Chromosomes 13, 14, 15, 21, 22
acrocentric (look one-armed)
Chromosomes 1,9,16, Y
heterochromatic region (tightly coiled, polymorphic)
repeats of ribosomal genes, polymorphic, acrocentric
satellite region
repeated info in the centromere
alpha satelite
repeated info just next to centromere
classical satellite
first unique sequence just next to telomere
telomeric sequences
large region colored (unique gene sequences)
repeated region
visually compares sample DNA to control DNA
CGH: comparative genomic hybridization
noninvasive prenatal testing
sample fetal DNA in maternal blood
copy DNA using normal and dideoxynucleotides, ddn are marker and tell you last nucleotide in sequence
sanger sequencing
characterized by expansion of a CGG triplet repeat in the first exon of the FMR-1 gene on the long arm of the X chromosome
fragile X syndrome
usually involve acrocentric chromosomes, which cluster together during meiosis.
robertsonian translocations
effects number of copies of all chromosomes
-ploidy
effects number of copies of individual chromosomes
-somy
most common genetic anomaly in still-births, 10% one year survival
Trisomy 18
brushfield spots, GI obstruction, Alzheimer’s
additional complications of Down syndrom
only mild sterility, learning disabilities with speech
triple X
tall, thin, slight IQ reduction, low testosterone, sterile, breast growth
Klinefelter XXY
tall, acne, mild IQ reduction, no aggression increase
Klinefelter XYY
Greek warrior helmet
4p deletion Wolf Hirschhorn
Wolf Hirschorn and Cri du Chat are
partial deletions
Prader-Willi, Angelman, Williams, DiGeorge are
microdeletions (<1Mbp)
Paternal copy of 15q11.2 deleted
Prader-Willi
Maternal copy of 15q11.2 deleted
Angelman
Chromosome 7 microdeletion
Williams
Chromosome 22 microdeletion
DiGeorge
translocation where an acrosome is lost
robertsonian
When the information in region 15q11-q13 is derived only from a mother (either via uniparental disomy (both chromosomes from a single parent) or deletion on the paternal chromosome
Prader-Willi syndrome (the maternally imprinted chromosome is unable to express its genetic information )
consists mainly of a satellite and a thin stalk, containing multiple copies of genes encoding ribosomal RNAs
short arm of an acrocentric chromosome
therapies that increase fetal hemoglobin may help these patients
Sickle-cell
both forms of hemophilia B are
promoter mutations
triplet that increases in earlier onset Huntingtons
CAG
genetic variations present at a particular locus
allele
deletions of alpha chain hemoglobin, 2 genes per chromosome, more deletions, more severe phenotype
alpha thalessemia
large population, random mating, no selection, mutation rate is constant, no im/emigration
Hardy-Weinberg assumptions
Heterozygote advantage of the AS genotype manifests as
better resistance to malaria
one locus, multiple normal alleles
polymorphism
when calculating odds of AR transmission, don’t forget
times one-half per parent (odds they will pass it)
different mutations in the SAME GENE cause similar phenotypes
allelic heterogeneity
different mutations in the SAME GENE cause different phenotypes
phenotypic heterogeneity
different mutations in DIFFERENT GENES cause same phenotype
locus heterogeneity
incomplete penetrance, variable expressivity, de novo mutation, germline mosaicism
AD pedigree problems
Known, micro: polymorphisms, insertions, deletions, NO heterozygotes
PCR
known, micro: deletions in heterozygotes
MLPA
known, macro: large scale deletions (>100bp)
Southern Blot
unknown, micro: determines sequence, NO short tandem repeats or copy-number variation
genome sequencing
unknown, micro: finds disease-causing genes, but stats may not be clinically useful (may identify marker, not gene of cause)
GWAS (Manhattan plots)
unknown, macro: detects chromosome-level changes such as copy number variation, NO <1 Mb
CGH (comparing sick and health genomes)
mRNA expressiong heatmapping, gene expression profile (cancer), BUT destroys architecture, can’t distinguish if expression is tumor cell or other cell
microarray
stains mRNA in tissue, can see gene expression in intact cells, but only a few at a time
RNA in situ hybridization
use antibody probe to determine if protein is being expressed, is right size, but destroys architecture
western blot
stain for protein with architecture intact, but can’t detect protein size
immunocytochemistry
sequence of 1-6 bps repeated many times
short tandem repeat (microsatellite)
sequence of 10-100bps repeated many times
variable tandem repeat (minisatellite)
good for CNVs but not microsatellites
array CGH. Use PCR and Sanger sequencing instead
detected with Guthrie assay (extra Phe on sample leads to bacterial growth)
PKU
detected with tandem mass spectrometry, avoid fasting!
MCADD
helps you rule out a disease
sensitivity (SNOUT)
helps you rule in a disease
specificity (SPIN)
methylation in a promoter region causes
DNA silencing
acetylation in a promoter region causes
increased DNA expression
still expressed on inactive X, helps to shut the X down
Xist
Mom wants it off, dad wants it on
Gene IGF2 (chromosome 11)
Mom wants it on, dad wants it off
Gene H19 (chromosome 11)
Oops, Mom turned IGF2 on (H19 normal)
Beckwith-Wiedemann: big baby
Oops, Dad turned on H19 (IGF2 normal)
Russell-Silver: small baby
imprinting diseases with epimutations
Russel-Silver, Beckwith-Weidman
imprinting diseases with real mutations
Prader-Willi, Angelman
mother’s allele is normally off (chromosome 15)
Prader-willi (need to get from dad)
father’s allele is normally off (chromosome 15)
Angelman (need to get from mom)
will have more methylation (which inactivates gene expression) and less acetylation (which activates gene expression)
inactive X chromosome
growth restricted genes are imprinted by
dad (to imprint=to turn OFF)
if monozygotic twins share a trait more often than dizigotic twins, that trait is
heritable
two genes segregate together due to proximity; one SNP is used to score a refion
linkage disequilibrium
under certain enviromental conditions, one genotype’s phenotype resembles another
phenocopy
different genes causing same phenotype (early and late onset Alzheimer’s, 18 genes responsible for cilia defects in Bardet-Beidl phenotype)
Genetic heterogeneity
smoking worsens prognosis in
alpha1 anti-trypsin disorder
In OI, missense mutation in α1 can lead to qualitative abnormalities in
¾ of type 1 collagen strands. Because of there are 2 α1 strands and 1 α2 strand in each collagen fibril, a mutation in α1 will cause defects in ¾ of the fibrils
The treatment for this condition is prenatal administration of cortisol, which prevents excess androgen production
congential adrenal hyperplasia
correct gene defects by gene addition, contain RNA
lentivirus vectors
