Midterm 1 Flashcards
% of liveborn babies with chromosomal abnormality?
1/120
when was number of chromosomes (46) in cell discovered?
1956
nucleosome core
147 bp DNA wrapped around 8 histone proteins 2X(H2A,H2B,H3,H4)
centromere makeup
satellites: repetitive DNA sequences. Heterochromatin
telomere composition
1-2k repeats of TTAGGG. Play role in synapsis
Are telomeric regions gene rich or gene poor?
gene rich
telomerase
reverse transcriptase that fills in last portion on lagging strand so chromosome does not shorten. Turned off in most adult somatic cells
aging syndromes
Hutchinson-Gilford Progeria Syndrome, Werner syndrome, Wiedemann-Rautenstrauch syndrome
nucleolar organizing regions
tandem repeats of rRNA genes found in stalk of all acrocentric chromosomes. Forms nucleolus, which combines rRNAs and proteins to form 40S and 60S ribosomal subunits
nucleolus
helps transcribe the rRNA genes and ultimately generates the ribosomal subunits (rRNA and proteins)
G-banding bands
Giemsa banding. Dark is AT rich (gene poor, heterochromatic) and light is GC rich (gene rich, euchromatic)
two main reagents needed for early chromosome counting
colchicine to arrest cells in metaphase, hypotonic solution
first autosomal trisomy to be discovered
Down syndrome. 1959
basic steps of preparing a karyotype
take blood, culture it, add cholchicine and hyptotonic saline, drop cells on slide, digest with trypsin, stain with Giemsa, analyze
will CGH microarray tell you copy number variants?
Yes, you compare to a reference sample and higher or lower expression will tell you
will a microarray detect a balanced translocation?
no
solenoid
coiling of nucleosomes
metacentric chromosome
p and q arms about equal length
submetacentric chromosome
small p arm
acrocentric chromosome
p arm is just a stalk and satellites (13,14,15,21,22)
composition of centromere
kinetochore, tandem repeats called satellite dna (distinct alpha satellites for each chromosome), heterochromatin
teleomere composition
role in synapsis- pairing in meiosis begins at subtelomeric regions. High gene density near telomeric regions. 1-2k TTAGGG repeats in telomeres
telomerase
reverse transcriptase. Turned off in most adult cells except certain blood cells and gonadal cells
origins of replication
sequence varies, but all have high AT content
NORs
Stalks of acrocentric chromosomes. Tandem repeats of rRNA genes. Forms nucleolus, which combines rRNA and proteins to make ribosome subunits
what are other types of banding stains?
R-banding (Reverse)
C-banding (constitutive heterochromatin)
T-banding (telomere)
Cd staining (centromeric dot or kinetochore)
NOR staining (nucleolar organizing regions)
In g staining, dark bands are…
A-T rich, late replicating, heterochromatic
in g staining, light bands are…
C-G rich, early replicating, euchromatic.
why does C-banding let you see Roberts syndrome?
c banding stains constitutive heterochromatin. In Roberts syndrome the heterochromatin (centromeres) repels from each other in sister chromatids, causing premature separation
In ISCN, in what order do you list abnormal chromosomes?
sex, then autosomal, starting with lowest
In ISCN, where do you put “mat” or “pat”
right after change. Ex: 46,XX,inv(14)(q12q31)pat
ISCN ::
break and rejoining
ISCN “add”
additional material of unknown origin
ISCN “r”
ring chromosome
ISCN “i”
isochromosome
ISCN “arr”
microarray
46,XX.ish 22q11.2(D22S75x2)
Interpretation: Female with normal karyotype by cytogenetic analysis and is normal by ish using a probe for locus D22S75
Interphase
G1, S, G2
Mitosis phases
prophase, metaphase, anaphase, telophase
2 sources of genetic variation in gametes
independent assortment, recombination
at what stage are oocytes arrested prior to menstruation?
prophase 1
what happens to oocyte during menstruation?
completes meiosis 1 and produces first polar body
Aneuploidy vs euploidy
aneuploidy is a difference from the normal 46. Euploidy is a difference in the set number
sources of aneuploidy
anaphase lag, nondisjunction, premature centromere division
most common autosomal trisomy
trisomy 16- but not compatible with life
Autosomal aneuploidies largely contributed by
mom
Mosaicism
more than one cell line, but all derived from same original zygote
Chimerism
distinct cell lines within an individual. Fusion of two conceptions. Usually confined to specific tissue(s)
does mitotic nondisjunction carry risk for UPD?
no
Recurrence of autosomal dominant disorders in multiple sibs born to normal parents may suggest
gonadal mosaicism
Cornelia de Lange syndrome features
eyebrows that meet in the middle, long eyelashes, short upturned nose thin downturned lips
ISCN rules for mosaicism
separated by slash. normal karyotype listed last. number of cells analyzed but in brackets
Isodisomy
inheritance of two copies of the same homolog from one parent
heterodisomy
inheritance of two different homologs from one parent
Mechanisms for generating UPD
Trisomy rescue, Gamete complementation, Monosomy rescue/mitotic duplication, Somatic crossing over
what % of viable pregnancies show confined placental mosaicism?
2%
nips lower limit of fetal fraction
4%
how long are fetal dna fragments in blood?
about 200 bases
whole chromosome aneuploidy usually from
mom
de novo balanced structural rearrangements usually from
dad? really?
deletion syndrome examples
cri du chat, Wolf-Hirschhorn, williams, Alagille, DiGeorge
duplication syndrome examples
beckwith-wiedemann, cat eye
paracentric inversions
do not include centromere. both breaks on one arm. can lead to dicentric and acentric chromosome in meiosis during crossover
pericentric inversions
include centromere. one break on each arm. generate chromosomes with one centromere in meiosis (normal)
most common structural rearrangement
robertsonian (13;14 most common)
telemere gene density
There is a very high density of genes at the telomeres, and recombination rates are higher at the telomeres than at other regions of the chromosomes. The end of each chromosome is capped with 3 - 20 kb of TTAGGG repeat.
Number of cross overs per meiosis
2.4 per chromosome pair for males. Higher for females
Nondisjunction
failure of chromosomes (during meiosis I) or chromatids (during mitosis or meiosis II) to separate at anaphase
Anaphase lag
failure of a chromatid or chromosome to attach to the spindle and segregate into a daughter cell
Parental origin of triploidy
85% paternal
Among couples with two or more SABs, X% of the couples will have a chromosome abnormality (usually a translocation or inversion).
6% of the couples (3% of individuals in those couples)
Placental mosaicism seen at CVS is associated with true fetal mosaicism ~X% of the time.
10% (still current?)
Breakdown of Down syndrome cause
85-90% maternal meiosis (75% M1, 25% M2)
3-5% paternal meiosis (25% M1, 75% M2)
4% robertsonian translocations (75% de novo, 25% familial, though depends on which robertsonian)
3-5% mitotic
Inversions: Small distal segments lead to ___ imbalances and___ (sometimes very large) risks.
Small distal segments lead to small imbalances and large risks.
Inversions: Large distal segments lead to ___ imbalances and relatively ___ risks for having liveborn abnormal children and ___ risks for period of infertility or miscarriages.
Large distal segments lead to large imbalances and relatively low risks for having liveborn abnormal children and high risks for period of infertility or miscarriages.
Partial ___ are usually more lethal than partial ___.
Partial monosomies are usually more lethal than partial trisomies.
___ segregation of a quadrivalent pairing will yield normal and balanced gametes
Alternate
Supernumerary marker chromsomes
Extra structurally abnormal chromsomes whose origin or makeup are not apparent by traditional cytogenetic analysis.
Potential gametes of large, direct insertions
Normal, balanced, del, or dup.
If quadrivalent forms in meiosis, an odd number of crossovers occur, can get gametes with del and dup
Potential gametes of pericentric inversions
Normal, balanced.
Uneven number of crossovers in meiosis can lead to gametes with del and dup
If distal segments are large, not likely to be viable
Potential gametes of paracentric inversions
Normal, balanced.
Recombinant offspring pretty much impossible because chromosome would have incorrect number of centromeres
