Introduction to Cytogenetics Flashcards
What is cytogenetics the study of?
Chromosomes
In humans, how many autosomal and how many sex chromosomes do we have (which ones)?
23 pairs of chromosomes (so 46 in total)
Autosomal= 1-22
Sex= X+Y
How are the chromosomes numbered?
In order of size (i.e 1 is the biggest)
What do the dark bands on chromosomes signify?
Gene poor areas
What do the paler regions of chromosomes signify?
Gene rich areas
Which arm of the chromosome is named ‘p’ and ‘q’?
p= petit (the shortest arm) q= long arm
Which phase of the cell cycle are chromosomes most detectable in and therefore used in molecular cytogenetics?
Metaphase
Describe the different stages of mitosis.
Interphase= condensation of chromosomes Prophase= Sister chromatids Prometaphase= Mitotic spindle start to form Metaphase= Mitotic spindles attach to centromeres Anaphase= Sister chromatids pulled apart Telophase= Membrane starts to separate Cytokinesis= Separation
What is ‘G-banding’?
A technique used to chemically inhibit the continuation of metaphase and staining the chromosomes to produce a clear karyotype- often useful for detecting disease
Why is cytogenetics so important- What % of still births, miscarriages and cancers have resulted from genetic disorders?
5% stillbirths
60% miscarriages
40% all conceptions
up to 100% cancers
There are over 140 different known syndromes and genetics has a major contribution to learning difficulties (around 20%)
Give 5 ways in which cytogenetic abnormalities produce abnormal phenotypes.
1) Dosage effect (loss or gain- loss is more deleterious than gain)
2) Disruption of a gene (inappropriate activation/inactivation, breakpoint)
3) Effect due to parental origin (Genomic fingerprinting- functional effect such as imprinted regions on chromosome 15)
4) Position effect (A gene in a new position functions inappropriately)
5) Unmasking of recessive disorder
The severity of phenotypes resulting from cytogenetic abnormalities varies, Many are lethal in utero. What phenotypes may arise to those who survive to be born?
Organ malformation
Facial dysmorphism
Compromised mental/intellectual functioning
Do abnormalities in the sex chromosomes lead to less or more severe phenotypes?
Much less severe than autosomal as they contain fewer genes
There can be structural or numerical abnormalities with chromosomes. Focusing on numerical, describe what the following sets are (healthy or abnormal) and what their individual chromosomes are called: Haploidy Diploidy Triploidy Tetraploidy Polyploidy
Both of these are normally found in humans:
Haploidy (gametes)= Monosomy
Diploidy= Disomy
The following are abnormalities:
Triploidy (3) = Trisomy (3 chromosomes- Such as in down syndrome)
Tetraploidy (4) = Tetrasomy (4 chromosomes)
Polyploidy (many-general)
What is Mosaicism?
Diploidy + aneuploidy at the same time
What are the three origins that may give rise to a numerical abnormality?
Gametogenesis
Fertilisation
Early cleavage in post-zygotic non disjunction
Gametogenesis can be an origin of numerical errors in chromosomes. As the mother’s age increases, what effect does that have on the chance of aneuploidy (presence of abnormal number of chromosomes in cells) occuring?
It increases, especially around late 40s- 1/3 chance of down syndrome. There is no risk as the father ages though
What is Chiasmata?
The process in which chromatids swap bits of DNA with their partners
Meiotic errors can lead to numerical errors (part of gametogenesis). Describe how.
Failure of chromosome or chromatid separation. In first stage of meiosis (meiosis 1), chromosome nondisjunction can happen where both chromosomes go into the same gamete instead of splitting, leading to two eggs being disomic and two being nullisomic. Chromatid non disjunction can occur in the second stage of meiosis (meiosis 2) which results in a disomic gamete, a nullisomic gamete and two normal gametes (look at slide if unsure)
Why are trisomy 21, 18 and 13 common but other types are not?
These are all survivable whereas others are not. E.g trisomy 19 is lethal as it has many pale parts/ gene rich areas and so is critical
What are the common names for trisomy 21, 18 and 13?
21: Down syndrome
18: Edward Syndrome
13: Patau syndrome
Trisomy 21: Down syndrome
How many babies are affected?
Which gamete and stage of meiosis causes this?
What percentage spontaneously abort?
1/700 90-95% trisomy 21, 80% maternal meiosis 1 2-5% mosaic - mitotic 2-5% Robertsonian translocation 75% spontaneously abort
What are the phenotypic features of trisomy 21 (down syndrome)?
Upslanting eyes Short neck Flat face Protruding tongue Low-set ears Sandal gap in toes Simian crease on hand
How does Trisomy 21 affect adults?
Fertility in males (usually infertile)
Average life span 55-68 yrs
Medical problems such as high risk of cancer, alzheimer’s, hypothyroid, obesity/coeliac, arthiritis, diabetes, hearing loss and seizures
