Genes, Chromosomes and Cell Division Flashcards
How are chromosomes organised?
- 22 pairs of homologous autosomal chromsomes identical in shape, size and number of genes
- 1 pair of sex chromosomes - heterologous
Define cytogenetics and what does it allow.
- Study of chromosomes and chromosomal abnormalities
- Allows visualisation of chromosomes e.g centromere position
Why is visualisation easier when the chromosomes are in metaphase?
- Chromosomes are condensed
Describe cytogenetic processing.
- Hypotonic solution added - causes nuclear swelling
- Staining to view bands
- Produces a karyogram
Give an example of banding used in karyotyping and what it can be used for.
- EXAMPLE: Giemsa banding
- Allows detections of rearrangements or deletions
What does 14q32 mean on a karyogram?
- Second band in 3rd region of long arm of chromosome 14
Describe FISH.
- Chromosomal DNA is unwound and separated into single strands
- Fluorescently labelled DNA probes bind to chromosomes
- Visualised under microscope
What can FISH be used for?
- Detect microdeletions or microinsertions
- Visualise chromosome organisation
Describe CGH.
- DNA extracted from specific patient cells and labelled green
- Reference DNA labelled with red fluorescent molecules
- Combine equal amounts and hybridise onto normal metaphase DNA array
How can CGH be used to detect chromosomal abnormalities?
- ABNORMALITY if ratio of green to red is unequal
- Can detect type/severity of cancers by scanning for deletions/duplications
Describe Array CGH and what are its advantages
.- Detects missing or duplicated pieces of chromosome
- Better resolution than FISH - detects microdeletions affecting only a single gene
- Can look at whole genome using small amount of DNA
What are the disadvantages of Array-CGH?
Cannot detect balanced chromosomal translocations
What is DNA sequencing used for?
- Determination of linear order of nucleotides of DNA
- Detection of indel mutations
How does DNA sequencing work?
- Complementary bases labeled by fluorescent dye specific for nitrogenous bases
- Specific nucleotides detected by colour
What are meiotic nondisjunctions?
- Two chromosome homologs migrate to same daughter cells instead of disjoining and migrating to different cells
Define aneuploidies.
- Missing or additional individual chromosomes due to nondisjunction
What is monosomy and trisomy?
MONOSOMY - one copy of chromosome in diploid cell
- TRISOMY - three copies
Describe Down Syndrome.
- TRISOMY 21 - Autosomal aneuploidy
What can trisomy 21 problems cause?
- Greater instances of heart septal defects, hypothyroidism, leukaemia etc.
Describe how Trisomy 21 (T21) conditons are diagnosed.
- Second trimester screening for AFP, hCG and the estriol steroid
- If baby at high risk, mother offered amniocentesis and chorionic villus sampling done by karyotyping/FISH
Describe Edward’s Syndrome.
- TRISOMY 18 - Autosomal aneuploidy
- Causes heart, GI and CNS defects
- Diagnosed through karyotyping
- Major cause of death is cardiac/respiratory failure - half don’t survive beyond first week
Describe Patau’s Syndrome.
- TRISOMY 13 - Autosomal aneuploidy
- Polydactyly, brain and spinal cord defects
- Diagnosed by karyotyping
- Prognosis is poor (80% don’t survive beyond one month)
Describe Turner’s Syndrome and how it can be inherited.
- X chromosome monosomy - sex chromosome aneuploidy
- Usually offspring receives X chromosome only from mother
- Absence of paternally derived sex chromosome during early mitosis in embryo/during meiosis in father caused by nondisjunction
What are the clinical features of Turner’s Syndrome?
- Affects females
- Ovarian dysgenesis
- Hand and feet lymphoedema
- Congenital heart defects
Describe Klinefelter’s Syndrome.
- Karyotype: 47, XXY
- Clinical features include hypogonadism, infertility, gynaecomastia
- X is from mother in 50% (NONDISJUNCTION AT MEIOSIS)
- Mosaicism in 15%
What is the difference between an unbalanced and balanced chromosome abnormalities?
- UNBALANCED - rearrangement causes gain or loss of chromsomal material
- BALANCED - does not do this
Describe reciprocal translocation
- TRANSLOCATION - interchange of genetic material between nonhomologous chromosomes
- Occurs during meiosis
- Breaks occur in 2 different chromosomes and material mutually exchanged
What is the result of reciprocal translocation?
- Inherit balanced/unbalanced translocation i.e partial trisomy/monosomy
Describe Robertsonian translocation
- Long arms fuse at centromere - form single chromosome
- Offspring may inherit missing chromosomes or extra long arm
Descibe insertion.
- One chromosome passes genetic material to another without reciprocal exchange
Describe inversions.
- Chromosome segment reversed end to end
- Single chromosome undergoes 2 breaks and reinserted in inverted order
- Can be peri- or paracentric
- Structural arrangements are balanced so carrier asymptomatic
How can inversions affect meiosis?
- Interfere with lining up of chromosomes
- Results in duplications/deletions in chromosomes of daughter cells
What is somatic mosaicism?
- Chromosome rearrangements in somatic cells
- Can cause cancer
Describe the Philadelphia chromosome.
- Translocation of most of C22 to long arm of C9
- Distal portion of 9q translocated to C22
- Protooncogene called ABL moved from normal position from 9q to 22q
- Alters ABL gene product - increased tyrosine kinase activity and malignancy in hamapoetic cells
