Case 13- chromosomes Flashcards
Homologous chromosomes
Two copies of the same chromosome. One is inherited from your mother and the other from your father
Centromere
The point at which the mitotic spindle attaches during mitosis and where the 2 chromatids attach during DNA replication, not always in the centre
P and Q arm of the chromosome
The P arm is the short arm of the chromosome the Q arm is the long arm of the chromosome.
Chromatids
In DNA replication you from two sister chromatids but because they are attached they are a chromosome.
Function of chromosomes
The main function of the chromosomes is to provide a storage mechanism for DNA (DNA packing) and allow DNA to be accurately distributed between cells during cell division.
Somatic human cell karyotype
46 chromosomes that are arranged in 23 pairs, one maternal and one paternal chromosome for each pair. Each pair forms a homologous chromosome because they determine the same genetic characteristics but they may not be identical genes. There are 44 autosomes and 2 sex chromosomes (X,Y)
Karyotype
The characteristics of the combined chromosomes (number, type etc)
Metacentric chromosomes
Where the centromere is in the centre, so the arms are equal length
Submetacentric chromosomes
Where the centromere is slightly to one side so the arms are unequal.
Acrocentric chromosomes
Where the centromere is quite far to one side, so the arms are unequal. May contain a chromatin satellite which is caused by a stalk which is a region of condensed chromatin which is hypermethylated. At the stalk the DNA is turned off, the satellite is the region beyond this.
Importance of Acrocentric chromosomes
They are commonly involved in chromosomal abnormalities like translocation errors
Main role of meiosis and mitosis
To maintain the number of 46 chromosomes in somatic cells
Types of chromosomal abnormalities
1) Numerical abnormalities
2) Structural abnormalities
Chromosomal abnormalities- Numerical abnormality terms
Aneuploidy is the gain or loss of one or more chromosomes. Trisomy is the gain of one chromosome, monosomy is the loss of one chromosome. Polyploidy is the addition of one or more complete sets of chromosomes.
Chromosomal abnormalities- Structural abnormalities
Translocation is the transfer of genetic information from one chromosome to another. You can also get insertions, deletions, inversions and ring chromosomes. Inversions are when the genes are switched to the wrong order. In the ring chromosomes the end of the chromosomes break off and become sticky and the chromosome forms a circle.
What causes aneuploidy
Non-disjunction errors during meiosis
Aneuploidy- problems in meiosis 1
Problems in Meiosis 1 results in 2 gametes with 1 more chromosome and 2 gametes with 1 less chromosome. When these gametes fuse with a healthy sperm/egg the embryo will have 47 chromosomes or 45 chromosomes.
Aneuploidy- problems in meiosis 2
Problems in Meiosis 2 causes 2 gametes which are normal, one gamete with an extra chromosome and a gamete with one less chromosome.
The only viable Monosomy
Turners syndrome- women who only have a single X chromosome
The viable Trisomy autosome syndromes
- Edward’s- chromosome 18
- Patau’s- chromosome 13
- Down’s- chromosome 21
Life expectancy with Trisomy disorders
People with Down’s syndrome can live to their 50’s or 60’s. Patau’s and Edward’s syndrome are a lot more severe and can result in still birth or the baby may die shortly after birth.
Sex chromosome abnormalities
• Triple X syndrome in females (XXX, XXXX)
• Kinefelter syndrome in males (XXY)
• XYY syndrome in males
Not very severe
Translocation
When part of one chromosome moves to another
Translocation effects
Translocation can occur either during meiosis or during the first mitotic division of the fertilised egg. Translocations can either be balances or unbalanced. Balanced translocations result in no loss of genetic material or genes, the patient would be unaffected. An unbalanced translocation is when genetic material is lost or results in triomsy.
Robertsonian Translocation
4% of triomsy 21 (Downs syndrome). Long arm of chromosome 21 translocates to chromosome 14. Short arm of chromosome 14 translocates to chromosome 21.
Significance of chromosomes 14 and 21
They are acrocentric chromosomes
Mechanism of action of Robertsonian translocation
1) The long arms of chromosome 21 and 14 join together
2) Short arms are lost but they contain non essential RNA
3) Balanced carrier- full copies of chromosome 14 and 21
4) Abnormal meiosis as translocation causes abnormal pairing and segregation due to the abnormal number of chromosomes.
5) This results in different types of gametes. So, the person with the disease would not show any symptoms but their children may be abnormal depending on the gametes produced.
6) They may have a child with down syndrome as they will have two copies of 21 and a copy of 14 in the egg cell.
Fragile X syndrome
Genetic condition caused by chromosomal abnormalities. There is a DNA mutation on the X chromosome. It increases the number of repeats of the DNA CGG triplet. A normal X chromosome only has 5-40 repeats, fragile X has more then 200 repeats. It is classified as a pre-mutation if the X chromosome has 55-200 repeats. They wont show symptoms but if they develop more mutations they will develop the disease.
Symptoms of fragile X syndrome
1) Learning disabilities, can vary from moderate to severe
2) Distinct features like a long face and prominent jaw
3) Seizures
4) Females carriers have less severe symptoms, they may have some facial features and mild learning disabilities
Characteristics of Turner’s syndrome- females with one X chromosome
- Random – not linked to maternal age
- Often diagnosed at age 8-14
- Symptoms include learning difficulties
Characteristics of Down’s syndrome- Trisomy 21
- Small risk with every pregnancy, risk increases with maternal age
- Most cases not inherited
- Familial Down syndrome is rare
- Everyone with Down syndrome has some degree of learning disability
The trisomy disorders screened for at birth
Down’s (21), Edward’s (18) and Patau’s (13) syndrome.
The NHS screening programme consists of
• Ultrasound nuchal translucency test.
• Maternal blood tests
• Risk factor analysis
None of these are definitive diagnostic tests
Second stage of screening for chromosomal abnormalities
If you are deemed high risk from these three tests you are offered either Chorionic villus sampling (12 weeks) or Amniocentesis (16 weeks). These are invasive tests which are definitive.
Chromosomal testing in the future
The maternal blood test NIPT, it looks at the babies blood within the mothers blood and then looks at the DNA to see the number of chromosomes. Not currently available on the NHS
Ethical considerations for chromosomal testing
Chorionic villus sampling and Amniocentesis have a risk of miscarriage. Consideration of terminating pregnancy, with Down’s this is more difficult as there is a wider range of symptoms and some people can live long lives, mostly independent. For amniocentesis because the test is done at 16 weeks abortion would involve inducing labour which can be quite traumatic for the parents.
Chromosome screening- Nuchal Translucency (NT)
Measures the nuchal pad at the back of the babies neck. The thicker the nuchal pad the higher the risk of chromosomal abnormalities.
Chromosomal blood test
NT is combined with maternal age and the blood tests to indicate risk of abnormalities. The blood test measures levels of two proteins: hCG and PAPP-A. Increased hCG and decreased PAPP-A is associated with down’s syndrome.
Chorionic villus sampling
Involves putting a catheter through the vagina and taking a sample of cells from the Chorionic villus which is at the placenta. The cells of the chorionic villus have DNA that is genetically identical to the baby.
Amniocentesis
Done between 15 and 20 weeks, it involves inserting a needle into the amniotic sac and taking a sample of the amniotic fluid. The amniotic fluid contains some of the fetus’ cells. You can use these cells to establish karyotype and other requested genetic abnormalities in the foetus.
Karyotyping and Cytogenetics
You take a sample of cells from the patient i.e. circulating lymphocytes, skin cells and amniocytes. The cells are stimulated to go through the cell cycle and are arrested in Metaphase so that the chromosomes are visible
Karyotyping
Chromosomes are lined up in size. Stained to give a specific banding pattern on each chromosome. They are then compared for abnormalities.
When can you undergo karytotyping
1) May be as a foetus if you suspect they have a learning disability
2) Can be as a child if they have symptoms of a learning disability
Cytogenetics
For example, FISH (fluorescence in situ hybridisation)- DNA probes bind to specific chromosome. The DNA sequence will be complementary to the specific chromosome. The probe is attached to fluorochrome which will light up in fluorescent light. FISH is used in cancer diagnosis, in some cancers translocation or deletion is common. You can see the number of chromosomes and if there is any translocations. You would use different colours for maternal and paternal chromosomes. So, you could see if there were extra chromosomes or if one was missing.
Genes affected in genetic disease
CGG triplet expansion - Fragile X syndrome
CTG triplet expansion- Myotonic dystrophy
HTT gene mutation - Huntington’s disease
15q11 deletion - Prader Willi / Angelman Syndrome
Loss of UBE3A - Angelman syndrome
