The human genome and chromosomes Flashcards
why is the human genome useful
- Useful for understanding the structure of genomes
- Understanding the biology of genomes
- Understanding the biology of disease
- Advancing the science of medicine
- Improving the effectiveness of healthcare
describe the structure of the nuclear genome
- 3.2x109 base pairs
- 20,000 protein coding genes
- 46 chromosomes
- Inherited from both parents
how many chromosomes does each somatic cell have
Each somatic cell has 46 chromosomes which are mostly clearly seen at the metaphase stage of the cell cycle
how can you identify chromosomes in the karyotype
using G bands
what are G bands
- staining technique used in karyotype, used to identify abnormalities in the chromosome
what is the short arm called (above the centromere) in the chromosome
p
what is the long arm called (below the centromere) in the chromosome
q
what does the centromere do and describe the structure
- Keeps sister chromatids together
- Attaches sister chromatids to microtubules
- Repetitive DNA
- Breaks during DNA replication
What does the G light band do and describe the structure
- Gene rich – has lots of genes compared to the dark ones which have a few genes
- GC-rich – lots of G and C nucleotides
- Early replicating
What does the G dark band do and describe the structure
- Gene poor
- AT rich – lots of A and T nucleotides
- Late replicating
what is an autosome
any chromosome that is not a sex chromosome and occurs in pairs
what are the sex chromosomes
XX female
XY male
what does diploid mean and how many chromosomes are in diploid cells
describes cells and nuclei or organisms in which each chromosome except the Y chromosome is represented twice
what does haploid mean and how many chromosomes are in haploid cells
Haploid are organisms that have a single set of unpaired chromosomes
what does aneuploidy mean
this is an abnormal number of chromosomes
Name the genes that you need to know
- COL5A2 (2) - collagen
- COL5A1 (9) – collagen
- HBA1 (16) - alpha globin for haemoglobin
- HBA2 (16) - alpha globin for haemoglobin
- BTK (x) - crucial role in B cell development
What are coding sequences
encode proteins, constitute about 1.6% of human genome
what are non-coding sequences
encode other molecules (such as tRNA and rRNA) and regulates coding DNA function. Encode intergenic regions and introns: include control elements (such as enhancers and promoters) and repetitive sequences (telomeres)
what are axons
regions of gene that encode protein sequences
what are introns
non coding regions between the exons in genes
what are control elements
sequences such as promoters and enhancers that regulate transcription
what are pseudogene
– non-functional copy of a gene, arises from gene duplication followed by deleterious mutation in one copy
what are repetitive sequences
– tandem repeats of closely related DNA sequences, constitute about 40% of human genome
describe the process of making RNA (transcription)
- Part of gene read from transcription start site – this is the point at which DNA starts to e read
- Transcirpted to pre-mrna include code from exons and introns
- Splicing gets to mRNA
- Then this goes through translation to make the protein
- In the upstream region there are the control elements these are the enhancer and promoter and they work together through chromatin looping.
- If there is a mutation in the enhancer region it can prevent the chromatin looping and silence a gene
what do the intergenic region contain
contain control elements such as enhancers and promoters
what do splicing signals do
they remove the introns from the mRNA
what do non coding RNAs do
they regulate messenger RNA
define disomy
this is two copies of a chromosome
define polyploidy
gain of one or more haploid chromosome sets
define monosomy
one copy of a chromosome
define trisomy
three copies of a chromosome
define tetrasomy
four copies of a chromosome
define deletion
part of a chromosome containing genes and regulatory sequences is lost
define duplication
this is when a piece of chromosome may be duplicated, over expression of genes can be harmful because too many of certain proteins or gene regulating nucleic acids may disrupt metabolism
define inversion
a section of a chromosome may break off turn through 180 degrees and then join again
- although all genes are still present some may now be too far away from their regulatory nucleotide sequences to be properly expressed
describe the sex chromosome diseases
turner syndrome
klinefelter syndrome
describe all chromosome diseases
- Triploidy
describe the key features of Down syndrome
- trisomy 21
- 1 in 700 births
- 60% aborted
- 20% stillborn
- Distinct facial appearance
- Marked muscle hypotonia as a baby (floppy)
- Learning difficulty
- Congenital heart malformations
- Have a single palmar crease
describe what can cause Down syndrome
- 95% have three separate copies of chromosome 21
- 4% have extra copy of chromosome 21 because of robertsonain translocation
- 1% have mosaicism with normal and trisomy 21 cell lineages milder features because of the presence of the normal cells, this occurs post zygotically
what is down syndrome due to
- Trisomies associated with an increase in maternal age
- Eggs held and crossing over stage in meipsis from approx. 6 months gestation
- Wear and tear with increasing maternal age
describe Edwards syndrome
- 1 in 3000 births
- Multiple malformations
- Clenched hands with overlapping fingers
- Die within first few weeks
- If survives sever mental retardation
describe patau syndrome
- 1 in 5000 births
- Multiple malformations
- Affects midline structures particularly incomplete lobation of brain, cleft lip, congenital heart disease
- Die within first few weeks
- If survives then severe mental retardation
describe klnefelter syndrome
- 47 XXY
- 1 in 1000
- Infertility
- Poorly developed 2ndy sexual charatstics
- Tall
describe Turner syndrome
- 45 X
- 1 in 5000
- 99% lost in pregnancy
- Short sature
- Primary amenorrhoea
- Congenital heart disease
How can you diagnose conditions prenatally
- amniocentesis
- chronic villus sampling
- non invasive techniques - for Down syndrome
describe amniocentesis
- Genetic testing of cells from the amniotic fluid
- Ultrasound guidance – transabdominal sampling
- 15-18 weeks
describe chronic villus sampling
- Genetic testing of tissue from the placenta
- Ultrasound guidance – trans-abdominal or trans-cervical sampling
- 12-14 weeks
describe non-invasive techniques
- For down syndrome:
- Ultra sound imaging of nuchal translucency
- 11-14 weeks
describe the X chromosome
- Contains 1100 genes
- One of the two x chromosomes is randomly inactivated, therefore adult female is a mosaic of clones containing one or other x chromosome in an active state
- Ensures that each somatic cell has only one functional x like in male somatic cells
- Pseudoautosomal regions do not undergo activations as they contain genes which are present on the Y chromosomes and are involved in development
describe the Y chromosome
- Variable in size
- Few genes
- Many repeat sequence
- Encodes the sex determining region of the y chromosome – SRY gene
- SRY encondes a protein that is a member of the HMG group of transcription factors
- SRY is responsible for male sex determination
- Other genes on the Y chromosome are also important for male determination
Describe X inactivation
- Xist is a long non-coding RNA which is encoded in the X inactivation centre on the X chromosome
- Xist joins to the X chromosome from which it is expressed,
- This leads to chromatin changes and spatial reorganisation of the chromosome leading to transcriptional inactivation and formation of the BARR BODY
- males have no Barr bodies and females have 1 Barr body
- X inactivation is reversed only in the germ cells
- Barr Bodies indicate the number of inactive chromosomes
what does a telomere do
- Protective DNA and protein cap
- Repetitive DNA – same sequence over and over again (TTAGG) and protein
- Prevents DNA damage and chromosome fusion
describe translocation
joining one part of a chromosome to a second chromosome, in a balanced translocation part of the second chromosome joins to the first chromosome so there is no net gain or loss of material
describe robertsonain translocation
two chromosomes joining at their centromeres
Name the autosome causing diseases
- Down syndrome
- Edwards syndrome
- Patau syndrome
