11.

1 Basic patterns of human inheritance

The inheritance of a trait over several generations can be shown in a pedigree.
 Knowing a purebred dog’s ancestry can help an owner to know about health
problems common to that dog e.g. Canine Hip Dysplasia is a genetic disease and is
most commonly seen in large breed dogs (> 22 kg).
 Similarly you can trace human inheritance to show how a trait is passed one from
one generation to the next.
Recessive Genetic Disorders
As explained before Mendel’s work was ignored for more than 30 yrs.
In the early 1900’s scientists became interested in heredity and his work was rediscovered.
At about this time, Dr Garrod became interested in
alkaptonuria – Caused by an enzyme deficiency leading to
the excretion of an acid into the urine which becomes black
when it is exposed to oxygen. Starts at birth and continues
through a patients life affecting their joints and bone. It runs
in family and with the help of another scientist they worked
out that it was caused by a recessive genetic disorder.
AKU_DIP_EN_0.pdf (sjdhospitalbarcelona.org) This source provides easy to read and interesting
information on this disorder if you are interested.
Remember that a recessive genetic disorder is expressed when the individual is
homozygous recessive for that trait i.e. aa. And to be homozygous recessive, this person
must have inherited that allele from his father and from his mother.
Recessive genetic disorders
Cystic fibrosis – taaislijmziekte
Bronchiectasis - Saltwonder

 One of the most common genetic disorders. 1 in

3500 births in the US.
 The gene that codes for a certain membrane protein
has undergone a mutation.
 Chloride ions are not properly transported out of cells. This increases the osmotic
concentration and so water does not diffuse out of cells.
 This affects the cells that produce mucus, sweat and digestive juices. Normally these
fluids are thin and slippery but in people with CF, the secretions are thick and sticky,
clogging up tubes and ducts particularly in the lungs and in the pancreas.
 It leads to digestive and respiratory failure.
 There is no cure. Treatment is physical therapy, mucus thinning drugs, enzyme
supplements.
Inheritance of a recessive disorder
CF allele is f and the normal allele for the membrane protein is F
Parental phenotype Healthy carrier of CF allele x Healthy Carrier of CF allele
Parental genotype Ff x Ff
F f
F FF Ff
f Ff ff
The chance is ¼ or 25% that an offspring will be born with this disorder. Clearly you can
have 4 healthy kids too.

Albinism
 1 in 17000 births in the US
 A mutated gene results in the absence of a skin pigment
called melanin in the hair, skin and eyes.
 Can occur in animals too.
 Vision impairment is a key feature of all types of albinism.
 Need to be very careful in the sun. Skin is easily damaged
by UV radiation.

Albino dieren, foto's van albino dieren, Pauw - beelden (nature-pictures.org)

Galactosemia
 1 in 50 000 -70 000 births
 There are mutations in the GALT
gene resulting in the deficiency of
an enzyme.
 As a result galactose (a
monosaccharide sugar) and
galactose related compounds
accumulate in the body.
 There is no cure. Must restrict
galactose and lactose (milk sugar
which is digested to glucose and
galactose in the digestive tract) in
the diet.
 It causes mental disability, an enlarged liver and kidney failure
Galactosemia Information | Mount Sinai - New York
Tay-sachs disease
 1 in 2500 people are affected in the US. It seems to be predominant in Jewish people
of eastern European descent. Apparently in the US, 1 in 27-30 Ashkenazi Jews are
recessive carriers.
 A gene on chromosome 5 has undergone changes and an enzyme needed to break
down fatty substances is missing.
 Fatty deposits called gangliosides build up in the brain causing mental disability and
death by age 5. The baby is born healthy but within a few months becomes affected
by the disorder
----------------------------------------------------------------------------------------------------------------------
Dominant genetic disorders
Some genetic disorders are caused by dominant alleles. Then you need inherit only one
allele from one of the parents and the disorder presents itself.
Huntington’s disease Huntington's Disease:
Signs, Symptoms, Complications (verywellhealth.com)

 Occurs in 1 in 10 000 people in the US.

 It affects the nervous system and first
appears in affected people at ages 30-50.
 People may have had children by that time.
 Genetic tests exist to detect this disease.
 There is a gradual loss of brain function,
uncontrollable movement and emotional disturbances. There is no cure
Inheritance of a dominant genetic disorder
Huntington allele is H and the normal allele is h
Parental phenotype Healthy person X Person with Huntington
Parental genotype hh x Hh
h h
H Hh Hh
h hh hh

Achondroplasia
 It is the most common form of dwarfism occurring in 1 in 25 000 births in the US.
 The arms and legs are short while the torso is a normal size. The average adult
height is 1.31m for men and 1.23 m for women. The life expectancy is normal.
  Apparently 75 % of individuals born
with achondroplasia, are borne to
parents of average size. That is the
result of a new mutation.
 Mutations have occurred in a gene
which codes for a protein necessary for
bone growth and maintenance.
 This protein is overactive, interfering
with normal skeletal development
 Wee man of Jackass fame has this disorder.
Where are the Jackass cast now? (thesun.co.uk)

Pedigrees
 In the case of plants or animals with lots of offspring e.g. fruit flies, scientists can do
crosses to determine the inheritance of traits.
 In the case of humans the family history can be studied with the aid of a pedigree. A
diagram that traces the inheritance of a trait through several generations. Symbols
are used.

 Males and female are always squares and circles respectively

 The one who expresses the trait is typically colored in i.e. colored square or circle.
Carriers may be indicated by half colored squares or circles.
 The horizontal line indicates the parents. The line below, the offspring of the parents.
 Offspring in a generation are in birth order from left to right. Numbered in Arabic
numerals
 Roman numeral indicate generations: Grandparents, Parents, Children.
 e.g Individual II 1 is a female who is the first born in generation II and does not have
the trait.
Pedigree analyzing a recessive disorder e.g. Tay-Sachs
 A pedigree analyzing Tay-Sachs is shown on the right.
 S = normal allele s = mutant allele
resulting in Tay-Sachs
 Two unaffected carrier parents (Ss)
have four children.
 Three do not have Tay-Sachs. They are
not even carriers.
 The third born child has inherited both
recessive alleles from his parents and has the genetic disorder. (ss)
 Always worth seeing if a “pedigree rule” applies here.

If two parents that are unaffected by a trait, have an offspring that has the trait, the parents
are heterozygous for the trait while the offspring is homozygous recessive
Pedigree analyzing a dominant disorder e.g. polydactyly
 People with this trait have extra fingers and toes. Polydactyly = P. Normal number = p
 Each unaffected person must be homozygous recessive for the trait i.e. pp.
 Unaffected parents (must be pp) cannot have affected children.
 Female I 2 must be heterozygous for the trait (Pp) since she has three children: II 3, 4
and 6 that do not have
the trait. They must have
inherited the recessive
alleles from her (Pp) and
from the unaffected (pp)
father I 1.
Inferring phenotypes
 Pedigrees help genetic counsellors to determine whether inheritance patterns are
dominant or recessive or even sex- linked (see 11.3).
 Dominant traits are easier to recognize than recessive trait because they are
expressed in the phenotype.
 A recessive phenotype will only be expressed if the person is homozygous recessive
for the trait.
 If good records are kept within families it may be possible to predict future disorders.
 Study of human genetics is difficult. It takes time for a generation to mature and to
have offspring.
Amish community reveal clues to manic depression - YouTube 5 mins Interesting film showing just this: