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

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

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

Down Syndrome

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

Skin fold over the eye.

Reduced mentalcapacity (varies greatly).

Short stature, stubbyfingers, and heart defects.

Down Syndrome Phenotype

Small and arched palate, large wrinkled tongue, dental anomalies

Slanting eyesEpicanthic eyefold

Broad flat face, short nose, flat back of head

Abnormal ears

Special skin ridge patterns. Many “loops” on fingertips. palm creases.

Enlarged colon

Umbilical hernia

Abnormal pelvis

Poor muscle tone

Big toes widely spaced

Intestinal blockage

Congenital heart disease

Absence of one rib on one or both sides

Short, broad hands

Edward SyndromeChromosome disorder: Trisomy 18

Incidence rate of 1 in6 000 live births (with aweak maternal age effect).

Females are affected morethan males (ratio of 1:2 ofmales: females)

Photo: C

ytogenetics Dept. W

aikato Hospital

Patau Syndrome

Chromosome disorder: Trisomy 13

Incidence rate of 1 in (approximately) 10 000 live births (with a maternal age effect). In most cases, fetuses are spontaneously aborted or are stillborn.

Photo: C

ytogenetics Dept. W

aikato Hospital

Maternal Age EffectMany aneuploidies show a ‘maternal age effect’, where incidence increases with the age of the mother.

Example:Down syndrome is 100 times more likely in children of mothers over 45 years, than in those of mothers less than 19 years.

Est

imat

ed r

ate

of

Do

wn

Syn

dro

me

(per

100

0 bi

rths

)

Maternal age in years

Maternal age(years)

< 3030 - 3435 - 3940 - 44

> 44

Incidence per1000 live births

< 11 - 22 - 55 - 1010 - 20

1 in 2 300 1 in 880 1 in 290

1 in 100

1 in 46

• The Y chromosome is a truncated X chromosome.

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.

Faulty Sperm Production

This results from failure of the X and Y chromosomes to separate during meiosis (non-disjunction).

Male Female

Primary spermatocyte

Mistake during meiosis

Faulty gametes

Offspring

Klinefeltersyndrome

Turnersyndrome

Klinefeltersyndrome

Turnersyndrome

XO

X

XX

XXY XOXXY

XYXY

XY

X X X X

X

XY

Faulty Egg Production

This results from failure of the two X chromosomes to separate during meiosis (non-disjunction).

X

X X

XY

XXXX

XXY

YY

YOXXX XO

Male Female

Primary oocyte

Mistake during meiosis

Faulty gametes

Offspring

Not viableTurnersyndrome

Klinefeltersyndrome

Metafemale

XXY

XX

Klinefelter Syndrome

Chromosome complement: 44 + XXY Poor beard

growth

Frequently some breast development (low levels of testosterone)

Chest hair is sparse

Penis and testes underdeveloped, low levels of testosterone. Always infertile.

Female type pubic hair pattern

Limbs tend to be longer than average

Osteoporosis

Sex chromosomes: XXY

Photo: C

ytogenetics Dept. W

aikato Hospital

Turner Syndrome

Chromosome complement: 44 + XO

Characteristic residual lateral web neck Low posterior

hair lineConstriction of aorta

Poor breast development

Degenerate ovaries (almost always infertile)

Reduced stature (body is typically short)

Brown spots (nevi)

Puffy fingers with deep set, hyperconvex fingernails

Elbow deformity

Sex chromosomes: XO

Photo: C

ytogenetics Dept. W

aikato Hospital

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

Thalidomide• 1957-1961

• Prescribed for morning sickness• Caused multiple abnormalities,

particularly to the limbs

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

Ultrasound (sonography)• Detects physical

abnormalities• Can also detect some

cases of Down’s syndrome

CVS (chorionic villus sampling) & amniocentesis

• CVS- • 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!

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