Atypical Inheritance

Bio 1
SDJacinto
Institute of Biology
UP Diliman
 Incomplete Dominance
Snapdragons - when homozygous red (RR)
snapdragons are crossed with homozygous white
(rr) plants, the F1 generation has the genotype Rr
and is pink. When these F1 plants are crossed, one
gets a ratio of 1 red (RR), 2 pink (Rr) and one
white (rr). Here the heterozygous phenotype is
intermediate between the two parents.
Carnations the same
 Codominance

Roan cow

Both alleles are

expressed but there
is no blending
 Polygenic traits
Determined by more than 1 gene
Human polygenic traits include
1. Height
2. SLE (Lupus)

3. Weight
4. Eye Color

5. Intelligence
6. Skin Color

7. Many forms of behavior

www.emc.maricopa.edu/.../ BioBookgeninteract.html
 Pleiotropy
- effect of one gene on more than one characteristic.
- Examples
- A. "frizzle-trait" gene in chickens
Primary result - production of defective
feathers
Secondary results -include increased adaptation
to warm temperatures, increased metabolic rate,
decreased egg-laying, changes in heart, kidney
and spleen

- B. white cats with blue eyes are often deaf, white

cats with a blue and an yellow-orange eye - deaf
on the side with the blue eye
fig.cox.miami.edu/~cmallery/ 150/gene/mol_gen.htm
Genetic basis of some
diseases
 Autosomal recessive inheritance

An abnormal gene on one of the autosomal

chromosomes (one of the first 22 "non-sex"
chromosomes) from each parent is required to cause
the disease. People with only one abnormal gene
allele are called carriers, but since the gene is
recessive they do not exhibit the disease.

In other words, the normal gene of the pair can supply

the function of the gene so that the abnormal gene is
described as acting in a recessive manner. BOTH
parents must be carriers in order for a child to have
symptoms of the disease; a child who inherits the
gene from one parent will be a carrier.
 Phenylketoneuria
About one in 10,000 children - born with
phenylketoneuria (PKU).

Caused by missing enzyme that breaks down

phenylalanine, one of the building blocks of the
protein found in a normal diet.

Serious if left untreated, causing mental impairment.

However, PKU is treated successfully by controlling
levels of phenylalanine in the diet.

All babies in the UK-heel-prick test shortly after birth. If

PKU is diagnosed babies are given a special diet.

Autosomal recessive inheritance

www.nlm.nih.gov/.../ ency/imagepages/2962.htm
 Tay-Sachs disease
Rare and extremely severe genetic condition affecting
the brain and nerves.

 A baby with Tay-Sachs disease appears normal at

birth, but development starts to slow down at about 6
months of age. Gradually, the child becomes blind,
deaf and paralyzed

 Children with Tay-Sachs disease usually die before

the age of five. There is no cure for this devastating
disorder, and no effective treatment.

 Autosomal recessive mode of inheritance

Other Autosomal Recessive (AR) diseases:

• Sugar intolerance: galactose, fructose, saccharose,

lactose.
• Most amino acid disorders : tyrosinosis, cystinosis,
leucinosis. albinism variants (except ocular albinism
which is RLX) etc…
• Several lipid metabolism diseases.
• Several disorders of hormone synthesis, mainly
thyroid and adrenal.
• Cystic fibrosis ( 1 in 22 of whites in UK are carriers of
CF- chrosomosome 7)
 Autosomal Dominance Defined
 A single, abnormal gene on one of the autosomal
chromosomes from either parent can cause certain
diseases. One of the parents will usually have the
disease (since it is dominant) in this mode of
inheritance. Only one parent must have an abnormal
gene in order for the child to inherit the disease.

Other Autosomal Dominant Diseases/Conditions :

•Achondroplasia
•Aniridia
•Polydactyly
•Adenomatous polyposis of the colon
 Marfan's syndrome
(disorder of the connective tissue )

mutation of the fibrillin gene-produces mutant fibrillin which

weakens tendons, connective tissues and ligament; every
person in affected family has unique mutation in fibrillin

causes skeletal defects typically recognized in a tall, lanky

person, exhibit long limbs and spider-like fingers

chest abnormalities, curvature of the spine

particular set of facial features including a highly

arched palate and crowded teeth.

cardiovascular abnormalities - most significant of the defects

(may include enlargement of base of aorta).

Autosomal dominant mode of inheritance

www.nlm.nih.gov/.../ ency/imagepages/9611.htm
www.healthopedia.com/.../ marfans-syndrome.html
Huntington's Disease (Huntington’s chorea)
Repeated trinucleotide CGG in chrom 4 mutated to
CAG -adds a string of glutamines (Gln) to the
encoded huntingtin protein; the abnormal protein
interferes with synaptic transmission in parts of
the brain and leads to death of these brain cells.
Symptoms: (observed with gradual progression of
disease)
•depression
•difficulty in speaking and swallowing
•occasional delusions, hallucinations
•cognitive decline
•rapid, jerky involuntary movements (chorea)
•obsessive compulsive disorders.
Autosomal dominant mode of inheritance
Family of 5 children whose mom (deceased, inset) had HD
www.curehd.org/
 Fragile X syndrome
(discovered in 1991)

Caused by full mutation of FMR1 gene

Other individuals are carriers- they have a small defect in
FMR1 ("premutation") but do not show symptoms.
Carrier men (transmitting males) pass the premutation to
all their daughters but none of their sons.
Each child of a carrier woman has a 50% chance of
inheriting the gene.
The Fragile X premutation can be passed silently down
through generations in a family before a child is
affected by the syndrome.
A premutation is susceptible to expansion after
passage through a female meiosis. The larger
the size of a premutation, the more the risk of
expansion to a full mutation in the offspring.
Male and female with premutation are not
affected but their offspring will be.
 Common Symptoms/Manifestations of Fragile X
-attention deficit and hyperactivity
-anxiety and unstable mood
-autistic-like behaviors
-long face, large ears, flat feet
-hyperextensible joints, especially fingers
-Seizures (epilepsy) affect about 25% of people with fragile X
 mental impairment, ranging from learning disabilities

to mental retardation

Boys - more severely affected than girls; most have mental

retardation
Girls-only 1/3 to 1/2 have significant intellectual impairment; the rest
have either normal IQ or learning disabilities.
Emotional and behavioral problems - common in both sexes;
Most boys and some girls have some symptoms of autism, but
many are very social and interested in other people.
Pattern of inheritance of the fragile X syndrome in one family. The number of times
that the trinucleotide CGG is repeated is given under the symbols. The gene is on the
X chromosome, so women (circles) have two copies of it; men (squares) have only
one. People with a gene containing 80–90 repeats are normal (light red), but this gene
is unstable, and the number of repeats can increase into the hundreds in their
offspring. Males who inherit such an enlarged gene suffer from the syndrome (solid
red squares). (Data from C. T. Caskey, et al.).

users.rcn.com/.../ BiologyPages/M/Mutations.html
www.nichd.nih.gov/.../ FragileX_cover.htm
 X-linked diseases

1. Phenotypic expression more common in

males
2. Sons cannot inherit the trait from their
fathers, but daughters can. Sons
inherit their Y chromosome from their
father.
Examples of X linked diseases/condition :

-Colour blindness
-Hemophilia A and B
-Duchenne muscular dystrophy
-Incontinentia pigmentosum
-G6PD deficiency
 Other genetic diseases
 Familial (Familial Adenomatous Polyposis)
 Multifactorial diseases (genetics and
environment have roles to play e.g.
cardiovascular, stroke, obesity )
 Genetic testing and counseling
 Some diseases tended to run in families
 Eugenics- study of how to improve human qualities
through directed breeding practices,
 Eugenicists felt that traits like intelligence, criminal
behavior and artistic ability could be traced to simple
dominant or recessive genes.
 By encouraging people with "good" traits to have
more children and encouraging people with "bad"
traits to have fewer or no children, eugenicists felt
they could rid the world of many social problems.
Although many rejected eugenics because of Nazi
horror, many still believed in it. Hence, the first medical
genetics clinics opened in the United States in the mid-
1940's and early 1950's

Medical geneticists conducted "hereditary counseling

clinics" with families, examined affected individuals and
drew pedigrees to help clarify the genetic component of
diseases and birth defects. They worked primarily with
relatively common diseases and conditions such as
sickle cell anemia, achondroplasia.

Only little genetic information at that time.

The practice of genetic counseling took a giant leap
forward in 1967 with the first amniocentesis.

Amniocentesis, while tremendously informative, is

not a fool-proof process. It carries risks including
potential infection and/or miscarriage. Also there are
limitations on what amniocentesis can predict about
the baby.

www.leighday.co.uk/ cat.asp?cat=972
www.bio.miami.edu/ dana/250/25003_10.html
Pedigree –
determines a person's risk of developing a
genetic disease
•helps make a diagnosis of a genetic disease,
•determines the risk of having a child with a
genetic disease

Pedigree includes relatives up to 3rd degree

- includes vital medical information-birth date,
age at death, cause of death, health problems, results
of genetic tests.

Pedigree on
alkaptonuria
Medical tests could be specialized like a
(chromosome study) or DNA
analysis (detect gene mutations) or
more general- X-ray, ultrasound, urine
analysis, skin biopsy, physical exam.

After medical tests genetic counselor may be able

to make a diagnosis, or determine a
person’s risk for a genetic disease.

Biggest challenge - help families cope with the emotional,

psychological, medical, social and economic consequences
of genetic disease.
 Newborn screening for genetic
disorders

gslc.genetics.utah.edu/ units/disorders/newborn/ www.doh.wa.gov/ ehsphl/phl/newborn/

Newborn screening for genetic disorders was started
in the US by Dr.Robert Guthrie for phenylketonuria.
There is now 100% implementation in the USA. In
Asia- Japan, Singapore, Hong kong, Taiwan and
Thailand also have 100% coverage.

Introduced in the Philippines in 1996 by the Newborn

Screening Study group. This includes now PKU,
congenital hypothyroidism (CH), congenital adrenal
hyperplasia (CAH), galactosemia and recently glucose 6
phosphate dehydrogenase (G6PD) deficiency

Local statistics state that at least 33,000 newborns are

saved annually from mental retardation and death due to
the screening
 Newborn Screening Act of 2004 in the
Philippines R.A. 9288
Requires that every baby born in the Philippines will
be offered a chance for newborn screening for the
5 disorders which may potentially prevent mental
retardation and death. Approved April 7, 2004
Despite govt and private efforts, only 3% of
newborn are screened. Lack of health professional
and public awareness of benefits of newborn
screening.
 Screening for 5 disorders-net annual benefit of

$12 M
That’s the last slide!!!!!
http://webexhibits.org/causesofcolor/2.html#vissamp