The Human Genome and Chromosomes Flashcards
the nuclear genome is made up of..
- how many base pairs?
- how many protein coding regions?
- how many chromosomes?
base pairs: 3.2 x 109 base pairs
protein coding regions: 25 000
chromosomes: 46
which stage of cell division can chromosomes most clearly be seen in?
metaphase (where chromosomes line up before seperated or divided)
describe and explain the structure of a chromosome
telomeres:
- at each end
- protective DNA cap.
- contains repetitive DNA
Centromere:
- found in centre
- keeps sister chromatids together and attaches them to microtubules
- repetitive DNA
- organised into short arm - p (petite) and long arm - q
what are the bands on chromosomes called? x2
what do they contain?
G-light band:
- Gene rich
- GC rich
- early replicating
G-dark band:
- gene poor
AT rich
Late replicating
which chromosomes are autosomes and which are sex chromosomes?
autosomes: 1-22
sex chr: 23 - XX - female, XY male
what is aneuploidy?
abnormal number of chromosomes
how are genes organised in a chromosome?
arranged in a linear fashion along each chromosome
describe the structure of a gene / what areas are found in a gene?
- exons: regions of genes that encode proteins
-
introns: non-coding sequences.
structure: exon followed by intron (exon, intron, exon etc)
- control elements: at the start of gene
describe v basic overview of DNA replication
- transcription of DNA
- creates: pre-mRNA
- splicing of pre-mRNA
- creates: mRNA
- translation of mRNA
- creates: protein
what are the different components of non sequencing bits of genes?
non coding sequences:
intergenic regions (regions between the exon/intron components), introns
control elements (e.g. promoters and enhancers - switch transcription on / off)
what are the following?
- aneuploidy
- polyploidy
- disomy?
- trisomy?
- monosomy?
- tetrasomy?
- aneuploidy: abnormal chr number
- polyploidy: gain of one or more haploid sets
- disomy: two copies of a chromosome
- trisomy: three copies of a chromosome
- monosome: one copy of a chromosome
- tetrasomy: four copies of a chromosome
what are the ways you can have abornmal chromsome structure?
chromomes can under go:
- deletion
- duplication
- inversion
- translocation (one part of a chr joins another part of a chr)
- Robertsonian translocation (two long arms of acrocentric chr (13, 14, 15 21, 22) join at their centromeres
give an example of where translocations can occur
in brain tumours - (e.g. glioblastoma multiforme)
from whom are autosome aneuploidy syndromes usually derived from?
maternally derived
name:
- three autosome aneuploidy syndromes
- two sex chromsomes aneuploidy syndromes
- one all chromosomes aneuploidy syndrome
- three autosome aneuploidy syndromes:
Down, Edwards and Patau syndromes
- two sex chromsomes aneuploidy syndromes:
Turner and Klinefelter syndrome
- one all chromosomes aneuploidy syndrome
Triploidy
name distinguishing features of Downs Syndrome and likely comorbidities
how many live births are DS?
What % of DS are spontanously aborted and still born?
stats: 1/700 births, >60% spontanously aborted, 20% still born
Features: Upward slanting eyes, marked muscle hypotonia (floppy), may have single palmar crease as child, learning difficulty, congenitial heart malformations (40%), Alzheimers (70% chance) - gene for APP
explain the three different patterns that can cause Down Syndrome
- trisomy 21: 95% DS - three copies of chr 21
- Robertsonian translocation (chrs 14 and 21): 4%. have an extra copy of chr. 21 due to aforementioned translocation
- Mosiacism: 1%. have normal and trisomy 21 cell linearges. occurs postzygotically. milder features (some cells have normal genome, some cells have trisomy 21 genome)
what are trisomies (particularly Downs Syndrome) associated with?
why does this risk factor cause DS ?
age (2.67/1000 @ 34 versus 71/1000 @ 48)
why?: eggs are held at corssing-over stage (prophase 1) in meiosis from approx. 6 months of gestation of the oocyte. wear and tear occurs at meiosis process with increasing maternal age
describe the symptoms and prognosis of Edwards and Patau syndrome
Edwards Syndrome - trisomy 18: multiple malformations (esp. heart). clenched hands with overlapping fingers)
Patau syndrome - trisomy 13: multiple malformations. Particularly: incomplete lobation of brain, cleft lip
In both: most babies die in first few weeks of life. if not - severe mental retardation
describe Klinefelter syndrome?
Klinefelter syndrome: (47, XXY). Extra X chromosome. Infertile - no sperm produced. Poorly developed secondary sexual characteristics, tall. 1/1000 males
describe Turner syndrome?
Turner syndrome -(45, X) Loss of X chr: 1/5000 females. 99% lost spon. in preg. short. abscence of menstruation (amenorrhea). congenital heart d: 20%. webbed neck
describe 3 prenatal diagnoses that can be undertaken to test for aneuploidy
- amniocentesis: genetic testing of amniotic fluid. using needle to extract transabdominal. 15-18 weeks of preg (risk to miscarriage: 1/100). ultrasound guidance used. t
2. chorionic villus sampling: genetic testing of tissue from placenta (choroinic villi), ultrasound guidance used transabdominal or transcervical. 12-14 weeks
3. non invasise technqiues: ultrasound imaging of back of neck of embryo at 11-14 weeks. if depth of fluid at back of neck is 3.5-4.4 mm = 70% chance of delivering baby with no major abnormalities.
what is X-inactivation?
early on in embryonic development, one of the two X-chr in each cells is randomly inactivated = X-inactivation or lyonization
The level of gene activity produced by a single X chromosome is the normal “dosage” for a human. Men have this dosage because, well, they only have one X chromosome! Women have the same dosage for a different reason: they shut down one of their two X chromosomes in a process called X-inactivation.
In X-inactivation, an X chromosome is compacted (or, as my intro bio professor liked to say, “crumpled up into a ball”), to make a small, dense structure called a Barr body. Most of the genes on the Barr body are inactive, meaning that they are not transcribed.
A woman has two X chromosomes, one from each parent. Which one will she inactivate? X-inactivation is a random process that happens separately in individual cells during embryonic development. One cell might shut down the paternal X, while its next-door neighbor might shut down the maternal X instead.
what does x-inactivation cause in the adult female cells?
all adult female cells are a clone of either one active X chromosome or one inactive chromosome
how can you see the X-inactive region of female somatic cell when a person has undergone X-inactivation?
female somatic cells that have X-inactivation have Barr Bodies. represents inactive chromsome in female somatic cell. this type of chromatin is called heterochromatin
do pseudoautosomal regions of x-chromsome undergo inactivation?
No.
Pseudoautsomal regions contain genes that pair up with Y-chromosome during meiosis
what is Xist?
- X-inactivation is assisted / coded by non coding RNA: XIST (X inactivion centre)
- Xist assocates closely with the X-chr from which it is expressed -> leads to chromatin changes and spatial reorganisation of chr. chr will condense into Bar > results in transcriptional inactivation in that chr.
how can you reverse X-inactivation?
only reversed in germ cells, where there are 2 fully activated X chromosomes
What is the SRY region on the Y chromosome?
SRY = Sex Determining Region of Y-chr.
SRY encodes for proteins that is a member of the HMG (high mobility group transcription factorrs) group -> which in turn are responsible for switching on genes that determine male sex determination
