1. Title: Chromosomal mutations 01 November 2015 Learning question: what can go wrong in meiosis and how can this be detected? Homework: STUDY!!!

2. Key words Mutation Chromosome Trisomy Non-disjunction Klinefelter’s syndrome Turner’s syndrome Karyotype Amniocentesis Chronic villus sampling ultrasonography

3. Aims from specification (h) explain the use of fetal ultrasonography, amniocentesis and chorionic villus sampling (CVS) for detecting named disorders and assessing fetal development. The advantages and disadvantages of each technique should be outlined (HSW6a, 6b); (i) outline how a karyotype is produced and used to determine fetal sex and to diagnose chromosomal mutations, with reference to Turner’s and Klinefelter’s syndromes; (j) explain how chromosome mutations such as Turner’s and Klinefelter’s may occur during meiosis (with reference to non- disjunction only).

4. Problems in meiosis Meiosis produces gametes that are haploid – this means that they only contain half the genetic information needed On rare occasions, sex chromosome fail to separate during anaphase 1 or 2 Results in a gamete without a sex chromosome and another with 2 sex chromosomes When chromosomes do not separate properly, this is called non-disjunction

6. Turner’s syndrome The result of a gamete with no sex chromosome being fertilised by a gamete with an X sex chromosome XO The resulting child is a female with Turner’s syndrome

7. Turner’s syndrome 1 in 6000 females are born lacking another X chromosome Females are short, have a webbed neck, shield- shaped chest, underdeveloped breasts, may not menstruate and have cardiovascular and renal problems

8. Klinefelter’s syndrome Gamete with an X chromosome is fertilised by a gamete with both an X and Y chromosome Baby will be XXY and have Klinefelter’s syndrome

9. Karyotyping A karyotype is a photomicrograph of chromosomes from metaphase of mitosis, with the chromosomes arranged in a standard sequence, so that doctors can see if there is an abnormality of the number of chromosomes in the fetus To prepare a karyotype, fetal cells have to be obtained, by amniocentesis or chorionic villus sampling (CVS)

10. TestAmniocentesisChorionic villus sampling Procedure to obtain cellsHollow needle inserted into amnion in pregnant uterus; amniotic fluid with sloughed off fetal skin cells withdrawn Ultrasound scan (ultrasonography) carried out so needle does not damage the fetus or the placenta Tube inserted into vagina, through cervix and into uterus. Ultrasound scan used to show where placenta is Cells from fetal part of placenta obtained AdvantagesEnables parents to prepare for a child with an abnormality or to terminate the pregnancy Can be done from 10 weeks, so if parents decide to terminate the pregnancy it may be less traumatic DisadvantagesCannot be done until the 16 th week as before that the amniotic sac is not large enough 1% risk of causing a miscarriage 2% risk of causing a miscarriage

13. Making a Karyotype 1.Cells are cultured, under aseptic conditions, for about 3 weeks, so they are dividing by mitosis 2.Cells are arrested at the beginning of metaphase by adding colchicine, which inhibits spindle formation 3.The cells are placed in a solution of very high water potential, so that they swell and burst and chromosomes spread out from each other 4.A stain is added to make the chromosomes easily seen 5.These cells are observed under the microscope and a photograph is taken

14. Questions 1.Sometimes, a zygote forms with three sets (69) of chromosomes. This is not viable and it spontaneously aborts. Suggest how a zygote with 69 chromosomes can occur. 2.Some patients with Turner’s syndrome are found to have some cells with XO and some with XX or XY chromosomes. Such patients are called mosaics as they have two cell lines in their bodies. What does this suggest about when the non-disjunction of chromosomes occurred in these patients? 3.Karyotyping could show a chromosome abnormality and prospective parents may decide to terminate the pregnancy. What are the risks to be considered before opting for such as test? 4.Explain why human cells placed in very dilute salt solution will swell and burst

15. Answers 1.An egg is fertilised by two sperms 2.It occurred after fertilisation, in one of the cells in an early fetus, during the early mitotic division of the zygote. If the zygote was originally XY but divided unevenly so that one resulting cell had no Y chromosome, then half the cells will be XO and half XY. This well develop as Turner’s syndrome female. if the zygote was XX but divided so that one cell lost an X chromosome, the descendants of that cell will also be XO. 3.Could have a healthy fetus to be aborted. Chorionic Villus Sampling can be carried out earlier in the pregnancy and allow an earlier termination, but carries a greater risk than amniocentesis of causing a miscarriage. 4.Water enters by osmosis, down the water potential gradient, through the partially permeable membrane. There is no cell wall, so the cell swells and eventually bursts as the cell surface membrane ruptures.

16. Diagnostic screening for genetic diseases can involve examination of chromosomes or examination of the base sequence of specific genes. Some genetic diseases are caused by chromosomal mutations. (a)State what is meant by a chromosomal mutation...................................................................................................................................... Karyotypes may be used to diagnose chromosomal mutations. (i)Name the condition shown by this foetus............................................................................................................................ [1]

17. (ii)State how the karyotype shown in the diagram above differs from a normal female karyotype......................................................................................................................................................................................................................................................[1] (iii) Name one procedure that could have been used to obtain the foetal cells............................................................................................................................ [1] (iv) Outline the stages in the production of a karyotype from foetal cells....................................................................................................................................................................................................................................................... [3]

18. Chorionic villus sampling (CVS) is a technique that can be used to test for the presence of genetic disorders in a foetus. A doctor inserts a narrow tube through the cervix into the uterus and removes a sample of foetal cells from the chorionic villi of the placenta. (i)Name one genetic disorder that could be diagnosed using this test. [1]..................................................................................................................................... (ii)Amniocentesis is another test used to screen for disorders in the foetus. Suggest one advantage and one disadvantage of using amniocentesis rather than CVS. advantage...................................................................................................... disadvantage.................................................................................................. [2] (iii)A karyotype may be produced using chromosomes from cells collected during these tests. Describe how the karyotype from a foetus with Turner’s syndrome would differ from that of a normal female karyotype...........................................................................................................................................................................................................................................................................[2]