ALL THE THINGS Flashcards
What are the two numerical chromosomal abnormalities?
Polyploidy and aneuploidy
What is polyploidy?
affects 1% of conceptuses. Changes in the number of all chromosomes equally
What is aneuploidy?
affects 1 in 300 newborns. Changes in the number of one or multiple chromosomes (unequally)
What are some types of polyploidy?
triploidy and tetraploidy
What are some types of aneuploidy?
monosomy, trisomy, tetrasomy
Are numerical abnormalities of somatic chromosomes incompatible with human life?
NO!
Exceptions are 13, 18, 21
Numerical abnormalities where are more likely to be viable?
sex chromosomes
What is the most common origin for triploidy?
2 haploid sperm cells fertilize a haploid egg cell
What are two types of balanced structural chromosomal abnormalities?
translocation and inversion
What are two types of unbalanced structural abnormalities?
deletion and duplication
How does the DNA content “c” change during the cell cycle?
from 2c in G1 phase to 4c after S phase
What are the stages of Mitosis?
interphase, prophase, metaphase, anaphase, telophase, cytokinesis
What happens in prophase?
chromatin condenses into chromosomes
What happens in metaphase?
nuclear envelope disappears, chromosomes align at the equatorial plane
What happens in anaphase?
sister chromatids separate, centromeres divide
What is cohesin?
protein that holds the length of chromatids together
At what stage of mitosis, does cohesin bind to chromosomes?
prophase
At what stage of mitosis is cohesin removed?
metaphase
How is cohesin removed?
separase degrades it proteolytically at centromeres allowing separation of chromatids
At what stage of meiosis does crossing over occur?
Prophase I
In which meiosis are homologs separated?
Meiosis 1
In which meiosis are sister chromatids separated?
meiosis 2
Where can Mendel’s 3rd law be observed?
when homologs segregate independently in meiosis 1
What is cytogenetics?
study of human chromosomes, their structure, inheritance, and abnormalities
What is an individual’s chromosome constitution called?
karyotype
Describe the preparation of a karyotype
add phytohemagglutinin to stimulate T cell division; culture for 3 days; add colchicine to arrest cells in metaphase; spread cells onto slide by dropping; digest with trypsin then stain with Giesma; analyze the metaphase spread
What kind of banding pattern is seen after applying a Giemsa stain to chromosomes?
G-banding pattern
What is the p-arm of a chromosome?
short arm
What is the q-arm of a chromosome?
long arm
Where are the telomeres of a chromosome located?
at the ends
What is a metacentric chromosome?
centromere located in the middle
What is a submetacentric chromosome?
centromere is near the middle
What is an acrocentric chromosome?
centromere is located farther away from the middle
What are the important acrocentric chromosomes in humans?
13, 14, 15, 21, 22
What color are the bands after a chromosome is treated with Giemsa?
light and dark
Describe light chromosome bands
less condensed euchromatin that replicated early in S-phase
Describe dark bands
more condensed heterochromatin that replicates later in S-phase
You are given a chromosome location, 7 q 3 1 . 2; What information do you have here?
chromosome 7; q arm; region 3; band 1; sub-band 2
What do the symbols p and q mean when describing a karyotype?
short and long arm
What does cen mean?
centromere
What does del mean?
deletion
What does dup mean?
duplication
What does fra mean?
fragile site
What does i mean?
isochromosome
What does inv mean?
inversion
What does ish mean?
in situ hybridization
What does r mean?
ring
What does t mean?
translocation
What does ter mean?
terminal or end
What does / mean?
mosaicism
What does + or - mean?
indicates gain or loss of part of a chromosome
What does 47, XX, +21 describe?
an extra copy of chromosome 21, trisomy 21 or Down syndrome
For Case 7, the child with VSD and slow developmental milestones had what syndrome?
DiGeorge Syndrome
Where is the deletion manifested in DiGeorge syndrome?
22 q 1 1
What causes 95% of individuals to be born with complete trisomy?
meiotic nondisjunction
What causes 4% of individuals to have Down Syndrome?
Robertsonian translocations
What causes 1% of individuals to develop a mosaic form of trisomy 21?
mitotic nondisjuntion
– milder features
What features are common for the clinical presentation of Down Syndrome?
dysmorphic facies, upward sloping palpebral fissures, over-folded helix
What is nondisjunction?
failure of chromosomes or chromatids to segregate in M1 or M2
Can nondisjunction occur in either the mother or father, with either autosomes or sex chromosomes?
Yes, hypothetically
How many copies from one parent does an individual with trisomy receive?
2 copies instead of the usual 1
If the two chromosomes from this parent are identical (2 copies of the maternal or paternal chromosome) then where did nondisjunction occur?
Meiosis 2
If the two chromosomes from this parent are not identical (one maternal and one paternal chromosome) then where did the nondisjunction occur?
Meiosis 1
How can you pinpoint where nondisjunction occurs in monosomy situations?
It is impossible to determine without knowing what the parent’s genotypes are
Where does nondisjunction most often occur?
maternal meiosis 1
Will an individual survive with polyploidy such as triploidy?
No. Will not make it to term
For autosomal nullisomy (missing a pair of homlogs), where is the lethality assessed?
preimplantation
For autosomal monosomy, where is the lethality assessed?
lethal in the embryonic stage
For autosomal trisomy, where is lethality assessed?
usually embryonic or fetal lethal
Which types of trisomy may survive to term?
Trisomies 13 and 18
Are individual’s with trisomy 21 expected to survive? If so, for how long?
Yes, til age 40 or longer
Name trisomies 13, 18, and 21
Patau syndrome, Edwards syndrome, Down syndrome
What is the life expectancy of individuals with multiple X or Y chromosomes?
minor problems, normal lifespan
Individuals at risk of having Turner’s syndrome have what complications before and after birth?
Born 45, X. 99% will abort spontaneously. survivors have normal intelligence, with infertility and minor physical abnormalities
What is the clinical presentation of Patau syndrome?
cleft lip/palate; cardiac defects; genito-urinary and renal defects; mean survival 7 days
What is the clinical presentation of individuals with Edwards syndrome?
microcephaly, CND and cardiac malformations, prominent occiput (back of head), micrognathia (undersized jaw), overlapping finger, rocker-bottom feet, median survival 14.5 days
Turner’s syndrome is expressed how on a karyotype?
45, X
In what pregnancy complication are cases of Turner’s syndrome commonly seen?
miscarriages (~99% of them)
What is the clinical presentation of Turner’s Syndrome?
short stature, delayed pubertal development, amenorrhea
How can the complications of Turner’s syndrome be treated?
Estrogen supplementation
How is Klinefelter expressed on a karyotype?
47, XXY
What is the clinical presentation for Klinefelter syndrome?
secondary sex characteristics display feminization; hypogonadims, infertility due to azospermia, disproportionately long limbs, tall thin stature
How are the complications of Klinefelter treated?
Testosterone supplementation
Does mental impairment increase or decrease as the number of X chromosomes increases in an individual?
increase
What happens to the additional X chromosomes in individuals with trisomies, etc?
All but one of the X chromosomes is inactivated. The rest form Barr bodies
Is there a gain or loss of genetic material with Balanced structural abnormalities?
No
Is there a gain or loss of genetic material with Unbalanced structural abnormalities?
Yes
Are individuals with balanced abnormalities generally affected?
No, unless the breakpoint occurs in or near a gene
Are the offspring of individual’s with balanced abnormalities at risk?
Yes
What are the two types of segregation that can occur during Meiosis?
alternate or adjacent segregation
Can alternate/adjacent occur in Meiosis 1 and Meiosis 2?
No! Just in meiosis 1
What kind of structural abnormality occurs from alternate segregation?
Balanced
What kind of structural abnormality occurs from adjacent segregation?
unbalanced
What is a translocation between 2 acrocentric chromosomes called?
Robertsonian translocation
What is lost in a Robertsonian translocation?
p arms are lost
What two things are retained in a Robertsonian translocation?
q arms and centromeres retained as fused chromosome
What kind of structural abnormality do Robertsonian translocations represent?
Balanced
What carrier karyotype is the most common for Down syndrome resulting from a Robertsonian translocation?
14 q 21 q
A balanced 14 q 21 q carrier has a ___ risk of having a live-born child with Down syndrome
1/3 (Possibilities are Normal, Balanced carrier, or Trisomy)
For 21 q 21 q balanced carriers, what are the 2 possible gametes?
Nullisomic for 21: monosomic offspring, lethal.
Disomic for 21: results in trisomy, Down syndrome
___ % of live-born offspring of a 21 q 21 q balanced carrier will have down syndrome
100
If 2 breaks occur in the same arm of a chromosome, what are the possible abnormalities that result? (What are the abnormalities called?)
Paracentric inversion
Interstitial deletion
If 2 breaks occur in different arms of a chromosome, what are the possible abnormalities that result? (What are the abnormalities called?)
Pericentric inversion
Ring Chromosome
Do Pericentric inversions involve the centromere?
Yes
What is not involved in a paracentric inversion?
the centromere
What are the two syndromes caused by autosomal deletions?
Wolf-Hirschhorn and Cri du Chat syndrome
What chromosome region is deleted in Wolf-Hirschhorn Syndrome?
4p- (4 p 1 6 is the critical region)
What facial abnormality is characteristic of Wolf-Hirschhorn syndrome?
broad flat nasal bridge, high forehead.
“Greek Warrior Helmet”
What chromosome region is deleted in Cri du Chat syndrome?
5p-
What is the common clinical presentation of Cri du Chat syndrome?
cat - like - cry
What types of deletions are only detected via DNA probes?
Microdeletion syndromes
