Case 13- chromosomes

Question 1

Homologous chromosomes

Answer 1

Two copies of the same chromosome. One is inherited from your mother and the other from your father

Question 2

Centromere

Answer 2

The point at which the mitotic spindle attaches during mitosis and where the 2 chromatids attach during DNA replication, not always in the centre

Question 3

P and Q arm of the chromosome

Answer 3

The P arm is the short arm of the chromosome the Q arm is the long arm of the chromosome.

Question 4

Chromatids

Answer 4

In DNA replication you from two sister chromatids but because they are attached they are a chromosome.

Question 5

Function of chromosomes

Answer 5

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.

Question 6

Somatic human cell karyotype

Answer 6

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)

Question 7

Karyotype

Answer 7

The characteristics of the combined chromosomes (number, type etc)

Question 8

Metacentric chromosomes

Answer 8

Where the centromere is in the centre, so the arms are equal length

Question 9

Submetacentric chromosomes

Answer 9

Where the centromere is slightly to one side so the arms are unequal.

Question 10

Acrocentric chromosomes

Answer 10

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.

Question 11

Importance of Acrocentric chromosomes

Answer 11

They are commonly involved in chromosomal abnormalities like translocation errors

Question 12

Main role of meiosis and mitosis

Answer 12

To maintain the number of 46 chromosomes in somatic cells

Question 13

Types of chromosomal abnormalities

Answer 13

1) Numerical abnormalities

2) Structural abnormalities

Question 14

Chromosomal abnormalities- Numerical abnormality terms

Answer 14

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.

Question 15

Chromosomal abnormalities- Structural abnormalities

Answer 15

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.

Question 16

What causes aneuploidy

Answer 16

Non-disjunction errors during meiosis

Question 17

Aneuploidy- problems in meiosis 1

Answer 17

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.

Question 18

Aneuploidy- problems in meiosis 2

Answer 18

Problems in Meiosis 2 causes 2 gametes which are normal, one gamete with an extra chromosome and a gamete with one less chromosome.

Question 19

The only viable Monosomy

Answer 19

Turners syndrome- women who only have a single X chromosome

Question 20

The viable Trisomy autosome syndromes

Answer 20

• Edward’s- chromosome 18
• Patau’s- chromosome 13
• Down’s- chromosome 21

Question 21

Life expectancy with Trisomy disorders

Answer 21

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.

Question 22

Sex chromosome abnormalities

Answer 22

• Triple X syndrome in females (XXX, XXXX)
• Kinefelter syndrome in males (XXY)
• XYY syndrome in males
Not very severe

Question 23

Translocation

Answer 23

When part of one chromosome moves to another

Question 24

Translocation effects

Answer 24

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.

Question 25

Robertsonian Translocation

Answer 25

4% of triomsy 21 (Downs syndrome). Long arm of chromosome 21 translocates to chromosome 14. Short arm of chromosome 14 translocates to chromosome 21.

Question 26

Significance of chromosomes 14 and 21

Answer 26

They are acrocentric chromosomes

Question 27

Mechanism of action of Robertsonian translocation

Answer 27

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.

Question 28

Fragile X syndrome

Answer 28

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.

Question 29

Symptoms of fragile X syndrome

Answer 29

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

Question 30

Characteristics of Turner’s syndrome- females with one X chromosome

Answer 30

• Random – not linked to maternal age
• Often diagnosed at age 8-14
• Symptoms include learning difficulties

Question 31

Characteristics of Down’s syndrome- Trisomy 21

Answer 31

• 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

Question 32

The trisomy disorders screened for at birth

Answer 32

Down’s (21), Edward’s (18) and Patau’s (13) syndrome.

Question 33

The NHS screening programme consists of

Answer 33

• Ultrasound nuchal translucency test.
• Maternal blood tests
• Risk factor analysis
None of these are definitive diagnostic tests

Question 34

Second stage of screening for chromosomal abnormalities

Answer 34

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.

Question 35

Chromosomal testing in the future

Answer 35

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

Question 36

Ethical considerations for chromosomal testing

Answer 36

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.

Question 37

Chromosome screening- Nuchal Translucency (NT)

Answer 37

Measures the nuchal pad at the back of the babies neck. The thicker the nuchal pad the higher the risk of chromosomal abnormalities.

Question 38

Chromosomal blood test

Answer 38

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.

Question 39

Chorionic villus sampling

Answer 39

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.

Question 40

Amniocentesis

Answer 40

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.

Question 41

Karyotyping and Cytogenetics

Answer 41

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

Question 42

Karyotyping

Answer 42

Chromosomes are lined up in size. Stained to give a specific banding pattern on each chromosome. They are then compared for abnormalities.

Question 43

When can you undergo karytotyping

Answer 43

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

Question 44

Cytogenetics

Answer 44

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.

Question 45

Genes affected in genetic disease

Answer 45

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