Lecture #21 - Chromosomal aneuploidy and X inactivation Flashcards
What’s a karyotype?
How to make one?
A karyotype is an ordered, visual representation of the chromosomes in a cell
Take a blood sample, treat cells with mitogen, then colchicine, then stain (stops the cells in metaphase where we can view the chromosomes with stains to see - bands form because of the staining technique).
Colchicine - a drug which prevents the formation of spindles
So, the chromosomes can be grouped in the karyotype - expand on this.
What’re the A, B, etc in the karyotype?
What’re telocentric chromosomes?
What group can X chromosome be a part of but isn’t?
What’s the difference between locus, gene and allele?
- The way chrosomes are structured in each group is similar so they’re grouped together e.g. the position of the chromosome (or where the centromeres are)
________________________________________
- A: metacentric chromosomes - have centromeres near middle
- B: submetacentric chromosomes
- D and C: acrocentric chromosomes
- Telocentric chromosomes = centromere at the end (not in humans)
- X chromosome can be part of C but isn’t
____________________________________
- A locus = place on chromosomes that gene found at e.g. A, B, O are different genes at same locus - called alleles.
Down Syndrome:
- What rate?
- Particular case of what?
- Give me some of the phenotypes of down syndrome people
- Mothers above what age have what percentage of all cases?
Down Syndrome:
- 1/750 live births - most common chromosomal abnomality
- Particular case of aneuploidy - three copies of chromsome 21. This causes phentoypic differences
- Phenotypic differences:
- Stronger crease in the middle of palm + short & fat fingers
- some degree of mental retardation
- growth failure
- broad, flat face, shorter nose
- Congenital heart disease
- Enlarged colon
- Abnormal pelvis
- Intentinal blockage
- Umbilical hermia - Mothers above 45 have 40% of all the cases
Name the two methods of prenatal diagnosis of aneuploidy
- When can they be done?
- What’s the risk?
- How are they done?
- Special ish about the two?
Aminocentesis:
- 16 - 20w of pregnancy
- 0.1% risk of miscarriage
- Method:
- Sample of amniotic fluid can be taken starting at the 14th to 16th pregnancy then centrifugation
- Biochemical and genetic tests can be performed immediately on the fluid or later on cultured cells
- Fetal cells must be cultured for several weeks to obtain sufficient numbers for karotyping
Chorionic villus sampling (CVS)
- 10 - 13w
- 1% risk of miscarriage
- Method:
- Sample of chorionic villus tissue can be taken as early as the 8th to 10th week of preg
- Karyotyping and biochemical and genetic tests can be performed on the fetal cells immediately, providing results within a day or so - CVS detects 90% of the Downs but it does have a higher risk (and apparently it’s not as accurate?)
Nondisjuction
- ___% of Down Syndrome babies have 2 maternal or paternal chromsome ____?
- What is nondisjunction?
- 95% of Down babies have 2 maternal chromosome 21
- Nondisjunction is when either homologous chromosomes or chromatids don’t separate properly
PAY ATTENTION TO THIS SLIDE - THNX
Klinefelter Syndrome XXY
- Males or females?
- Some phenotypes
- What aneuploidy is this?
- Males
- Looks like:
- breast development
- tall stature
- lose chest hairs
- female pubic hair pattern
- testicular atrophy
- mental retardation
Turner Syndrome XO
- What is it?
- Phenotypic ish
1 . Only one X chromosome (normally, one of our X chromosomes are inactive anyway but we still need two clearly)
- Refer to the diagram bitch
Appreciate this
Okay so, almost all of one X chromosome in each cell in female mammals becomes inactivated during ______.
As a result, the cells of females and males have the same effective dose (one copy) of ______……Doasge compensation through _______ (lyonisation)
The inactive X in each cell of a female _______ into a compact object called a ______, which lies along ______ and it doesn’t get ______.
- How does cell know which X to make inactive?
- If a female is hetero for a sex-linked trait - what happens?
- X inactivation involves what?
- What gene becomes active only on the chromosome that will become Barr body?
Okay so, almost all of one X chromosome in each cell in female mammals becomes inactivated during early embryonic development.
As a result, the cells of females and males have the same effective dose (one copy) of most X-linked genes……Doasge compensation through X inactivation (lyonisation)
The inactive X in each cell of a female condenses into a compact object called a Barr body, which lies along the inside of the nuclear envelope and it doesn’t get translated.
- Barr body occurs randomly and independently in each embryonic cell present at the time of X inactivation so females are a mosiac of two types of cells: those with the active X from mum and cells with active X from dad.
- If a female is hetero for a sex-linked trait - about half her cells express one allele and the other express the other allele eg sweat gland thing
- X inactivation involves modification of the DNA and proteins bound to it (histones) and attachment of methyl groups (act as molecular markers to signal that this DNA shouldn’t be read). Structural protein groups added to bind errythang tigher.
- The XIST (X-Inactive-Specific-Transcript) gene becomes active only in the chromosome that will become the Barr body.
Appreciate
And appreicate this too
Eg hemophilia (colour blindness)
You’d think that half of cells in females are haemophilia and other half not but apparently the wild type enough for body or something so not half colour blind cells
Wait dafaq - the last question? Idek. This seems like bullshit.
B
B
D
