1. What can go wrong? Mistakes during meiosis  anueploidy
Problems in differentiation
Chemicals or radiation can cause birth defects
Genetic diseases
Random chance
Note: 5-10% of babies have some type of congenital birth defect

3. Karyotypes Karyotypes are a picture of the chromosomes
Since the chromosomes are only clearly visible during mitosis:
Cells are collected
Colchicine is used to halt them in mitosis
The chromosomes are photographed
They are arranged in pairs according to size and banding patterns

6. Trisomies An individual has 3 chromosomes from a pair, instead of 2
Trisomies of the larger chromosomes usually result in death in utero. There are only 3 trisomies which usually result in live births.
Trisomy 21 Down syndrome
1:700 children.
characteristic facial features, short stature; heart defects
usually some degree of mental retardation
Down Syndrome is correlated with age of mother
Trisomy 18 Edward’s syndrome
Trisomy 13 Patau’s syndrome

7. Down Syndrome
Trisomy 21
Incidence rate of 1 in 800 births in women giving birth at 30 to 31 years of age.

8. Down Syndrome Phenotype
Skin fold over the eye.
Reduced mental capacity (varies greatly).
Short stature, stubby fingers, and heart defects.
Slanting eyes
Epicanthic eyefold
Small and arched palate, large wrinkled tongue, dental anomalies
Short, broad hands
Broad flat face, short nose, flat back of head
Absence of one rib on one or both sides
Abnormal ears
Congenital heart disease
Special skin ridge patterns. Many “loops” on fingertips. palm creases.
Intestinal blockage
Enlarged colon
Umbilical hernia
Abnormal pelvis
Big toes widely spaced
Poor muscle tone

9. Edward Syndrome Chromosome disorder: Trisomy 18
Incidence rate of 1 in live births (with a weak maternal age effect).
Females are affected more than males (ratio of 1:2 of males: females)
Photo: Cytogenetics Dept. Waikato Hospital

10. Patau Syndrome Chromosome disorder: Trisomy 13
Incidence rate of 1 in (approximately) live births (with a maternal age effect). In most cases, fetuses are spontaneously aborted or are stillborn.
Photo: Cytogenetics Dept. Waikato Hospital

11. Estimated rate of Down Syndrome (per 1000 births)
Maternal Age Effect
Many aneuploidies show a ‘maternal age effect’, where incidence increases with the age of the mother.
1 in 46
Maternal age
(years)
Incidence per
1000 live births
< 30
> 44
< 1
1 - 2
2 - 5
5 - 10
1 in 100
Example: Down syndrome is 100 times more likely in children of mothers over 45 years, than in those of mothers less than 19 years.
Estimated rate of Down Syndrome (per 1000 births)
1 in 2 300
1 in 880
1 in 290
Maternal age in years

12. The Y chromosome is a truncated X chromosome.

13. Nondisjunctions of the sex chromosomes
Klinefelter syndrome (XXY)
Male sex organs; unusually small testes, sterile. Breast enlargement and other feminine body characteristics.
Turner’s syndrome (XO)
Phenotypically female, however they do not mature sexually during puberty and are sterile. Short stature.
XXX females
Healthy and fertile - usually cannot be distinguished from normal female except by karyotype.
XYY males
Individuals are somewhat taller than average and often have below normal intelligence.

14. Faulty Sperm Production
Male
Female
This results from failure of the X and Y chromosomes to separate during meiosis (non- disjunction).
Primary spermatocyte
Mistake during meiosis XY XX XY X X XY XY X X X X
Faulty gametes
Offspring
XXY XO
XXY XO
Klinefelter
syndrome
Turner
syndrome
Klinefelter
syndrome
Turner
syndrome

15. Faulty Egg Production
Male
Female
This results from failure of the two X chromosomes to separate during meiosis (non- disjunction).
Primary
oocyte XY XX
Mistake
during
meiosis X Y XX X X Y Y XX XX
Faulty gametes
XXX
XXY XO YO
Offspring
Metafemale
Klinefelter
syndrome
Turner
syndrome
Not viable

16. Klinefelter Syndrome Chromosome complement: 44 + XXY
Poor beard growth
Chest hair is sparse
Frequently some breast development (low levels of testosterone)
Osteoporosis
Penis and testes underdeveloped, low levels of testosterone. Always infertile.
Female type pubic hair pattern
Photo: Cytogenetics Dept. Waikato Hospital
Limbs tend to be longer than average
Sex chromosomes: XXY

17. Turner Syndrome Chromosome complement: 44 + XO Sex chromosomes: XO
Characteristic residual lateral web neck
Low posterior hair line
Constriction of aorta
Poor breast development
Elbow deformity
Degenerate ovaries (almost always infertile)
Photo: Cytogenetics Dept. Waikato Hospital
Puffy fingers with deep set, hyperconvex fingernails
Reduced stature (body is typically short)
Brown spots (nevi)
Sex chromosomes: XO

18. Teratogens
Chemicals which affect embryonic development and cause birth defects
Foetal alcohol syndrome
Alcohol crosses the placenta
More vulnerable during early pregnancy
Causes:
Growth retardation
Brain damage
Skull and facial abnormalities

19. Thalidomide 1957-1961 Prescribed for morning sickness
Caused multiple abnormalities, particularly to the limbs

20. Pre-natal genetic diagnosis
This can be carried out via:
Ultrasound (e.g. spina bifida)
CVS (chorionic villus sampling)
Amniocentesis
Pre-implantation genetic diagnosis
Following IVF, 1 cell is removed from the embryo at the 8 cell stage
The DNA from the single cell is replicated & tested for genetic diseases

21. Ultrasound (sonography)
Detects physical abnormalities
Can also detect some cases of Down’s syndrome

22. CVS (chorionic villus sampling) & amniocentesis
Tissues are taken from the chorionic villus
Genetic testing is carried out
Weeks 10-11
Amniocentesis
Amniotic fluid containing shed cells from the foetus is sampled
Weeks 16-18
But there is a 1/100 risk of miscarriage!

24. What if the developing child has a genetic condition?
Termination- legal/ethical issues
Surgery in utero- to correct conditions like spina bifida
Preparing parents for life with a disabled child