Dominantly

Inherited Disorders
by: Jeffamie M. Bernilla
Bsed Sci 3-A
 DEFINITION

Achondroplasia
The term "achondroplasia" is derived from the Greek
words "a" (without), "chondro" (cartilage), and "plasia"
(formation). Therefore, it literally means a condition
where cartilage fails to form properly. In individuals
with achondroplasia, there's an abnormality in bone
development, particularly in long bones.

https://medlineplus.gov/genetics/condition/achondroplasia/
CAUSE
Achondroplasia is primarily caused by a
specific mutation in the FGFR3 (Fibroblast
Growth Factor Receptor 3) gene. FGFR3
provides instructions for creating a protein
involved in bone growth and development. In
achondroplasia, a single nucleotide substitution
in the FGFR3 gene leads to a gain-of-function
mutation, causing overactivity of the FGFR3
protein.
 HOW ACHONDROPLASIA INHERITED

Achondroplasia is inherited in an autosomal

dominant pattern. This means that if a person
has a mutation in one copy of the FGFR3 gene
(inherited from either parent), they will have
the condition.
 HOW ACHONDROPLASIA INHERITED
“A” normal allele Parent 1 (Father): Aa (heterozygous for the Achondroplasia mutation)
“a” mutated allele Parent 2 (Mother): Aa (heterozygous for the Achondroplasia mutation)

Child 1:
Inherits allele "A" from Parent 1 and allele "A" from Parent 2.
Genotype: AA
Phenotype: Normal, unaffected by Achondroplasia.
Child 2:
Inherits allele "A" from Parent 1 and allele "a" from Parent 2.
Genotype: Aa
Phenotype: Heterozygous carrier, unaffected by Achondroplasia but can pass the mutation to future generations.
 HOW ACHONDROPLASIA INHERITED
“A” normal allele Parent 1 (Father): Aa (heterozygous for the Achondroplasia mutation)
“a” mutated allele Parent 2 (Mother): Aa (heterozygous for the Achondroplasia mutation)

Child 3:
Inherits allele "a" from Parent 1 and allele "A" from Parent 2.
Genotype: aA
Phenotype: Heterozygous carrier, unaffected by Achondroplasia but can pass the mutation to future generations.
Child 4:
Inherits allele "a" from both parents (one from each).
Genotype: aa
Phenotype: Homozygous for the Achondroplasia mutation, affected by Achondroplasia and displays the characteristic features of
disorder.
 LOCATION IN CHROMOSOME
The mutation that causes achondroplasia is
typically found on chromosome 4. More
specifically, the mutation occurs in the FGFR3
gene located on the short arm of chromosome 4
 DOMINANCE OR RECESSIVE?
Achondroplasia is an autosomal dominant
disorder. A child who inherits one mutated copy
of the FGFR3 gene from either parent will have
the condition. If both parents have
achondroplasia (rare), the risk of having a child
with severe complications increases.
 DOMINANCE OR RECESSIVE?
In the case of achondroplasia: a person with one copy of the mutated FGFR3 gene
(heterozygous) will have achondroplasia (Aa) and exhibit the characteristic features of the
disorder. If both copies of the FGFR3 gene are normal (AA), the individual will not have
achondroplasia and will not be a carrier of the disorder.
 DOMINANCE OR RECESSIVE?
Assumptions:
The gene associated with Trait X is located on an autosome (a non-sex chromosome).
The dominant allele for Trait X is represented by "A," and the recessive allele is
represented by "a."

(Parent 1) who has Trait X and another parent (Parent 2) who does not have the trait but
is a carrier.
Genotypes:
Parent 1: Aa (affected with Trait X)
Parent 2: aa (carrier of Trait X, but unaffected)
 DOMINANCE OR RECESSIVE?
Possible Offspring Genotypes and Phenotypes:

Child 1:
Inherits "A" from Parent 1 and "a" from Parent 2.
Genotype: Aa
Phenotype: Affected with Trait X (dominant trait expressed).

Child 2:
Inherits "A" from Parent 1 and "a" from Parent 2.
Genotype: Aa
Phenotype: Affected with Trait X (dominant trait expressed).

Child 3:
Inherits "a" from both parents.
Genotype: aa
Phenotype: Unaffected by Trait X (homozygous for the recessive allele).
 Physical
characteristics
An average-size trunk,
short arms and legs with particularly short
upper arms and thighs,
limited range of motion at the elbows,
an enlarged head (macrocephaly) with a
prominent forehead.
Fingers are typically short and the ring
finger and middle finger may diverge, giving
the hand a three-pronged
 Huntington’s
Disease

https://medlineplus.gov/genetics/condition/huntingtons-disease/
Huntington’s Disease A progressive brain disorder that causes
uncontrolled movements, emotional problems,
and loss of thinking ability (cognition).
Huntington’s Disease is named after George
Huntington, who provided a detailed
description of the disorder in 1872. It is an
autosomal dominant genetic disorder, meaning
that an affected individual has a 50% chance
of passing the disease to their offspring. The
disease is caused by a mutation in the HTT
gene, located on chromosome 4.
CAUSE
Genetic Basis and Mutation
(HTT Gene):
The mutation in the HTT gene involves an
abnormal repetition of a CAG triplet in the
DNA sequence. This leads to an abnormal
protein called huntingtin, which is toxic to
nerve cells. The greater the number of CAG
repeats, the earlier the symptoms manifest
and the more severe the disease becomes.
Example of mutation
a. Normal HTT Gene:
CAG repeat in HTT gene: 20 repeats (normal range).
Genotype: A person with this genotype does not have Huntington's disease, and their huntingtin protein functions
normally.
Phenotype: No symptoms of Huntington's disease.
b. Mutated HTT Gene:
CAG repeat in HTT gene: 45 repeats (expanded beyond the normal range, causing HD).
Genotype: This individual has an expanded CAG repeat, resulting in the mutated huntingtin protein.
Phenotype: The individual will develop symptoms of Huntington's disease over time due to the toxic effects of the
mutant huntingtin protein on brain cells.
HOW HUNTINGTONS DISEASE INHERITED?
Huntington's disease is inherited in an
autosomal dominant pattern. If a person
inherits a single copy of the mutated gene
(HTT) from a parent, they will develop
Huntington's disease. Each child of an
affected parent has a 50% chance of
inheriting the mutation.
HOW HUNTINGTONS DISEASE INHERITED?

Affected Parent (Aa): An individual with Huntington's disease has one copy of the
mutated HTT gene (a) and one normal copy (A).
Unaffected Parent (AA): An unaffected individual has two normal copies of the HTT
gene (AA).
 Possible Offspring Genotypes and Phenotypes:
Child Inherits Mutated HTT Gene (Aa):
If a child inherits one copy of the mutated HTT gene (a) from the affected parent (Aa), and one normal copy (A) from the
unaffected parent (AA), the genotype is Aa.
Genotype: Aa
Phenotype: The child will be affected by Huntington's disease.

Child Inherits Normal HTT Gene (AA):

If a child inherits two normal copies of the HTT gene (AA) from both parents, the genotype is AA.
Genotype: AA
Phenotype: The child will not have Huntington's disease and will not pass it on to their descendants.

Child Inherits Both Mutated HTT Genes (aa):

It's important to note that individuals with two copies of the mutated HTT gene (aa) do not typically survive to adulthood due
to the severe effects of the disease.
Location of Huntington's Disease in Chromosomes

The huntingtin (HTT) gene associated with

Huntington's disease is located on the short
arm of chromosome 4 (4p16.3). The mutation
involves an expansion of CAG repeats within
this gene.
 Dominance or Recessive
Huntington's disease is an autosomal dominant
disorder. If an individual inherits one copy of
the mutated huntingtin gene (HTT), they will
develop the disease. A child of an affected
parent has a 50% chance of inheriting the
mutation and, consequently, developing
Huntington's disease.
 Dominance or Recessive

"A" for the normal allele (non-mutated) and

"a" for the mutated allele (causing Huntington's disease).

Parent 1 (Affected): Aa (heterozygous for the Huntington's mutation)

Parent 2 (Unaffected): AA (homozygous for the normal allele)
 Possible Offspring Genotypes and Phenotypes:
Child Inherits Mutated HTT Gene (Aa):
Inherits "a" from Parent 1 and "A" from Parent 2.
Genotype: Aa
Phenotype: Affected with Huntington's disease.

Child Inherits Normal HTT Gene (AA):

Inherits "A" from both parents.
Genotype: AA
Phenotype: Unaffected by Huntington's disease.
 Symptoms and Clinical Characteristics

1 Motor Symptoms:
Involuntary movements (chorea).
Difficulty in coordination and balance.
Rigidity.

2 Cognitive Symptoms:
Cognitive decline affecting memory,
reasoning, and concentration

3 Psychiatric and Behavioral Symptoms:

Involuntary movements (chorea).
Difficulty in coordination and balance.
Rigidity.
REFERENCES:

https://medlineplus.gov/genetics/

(https://hdsa.org/)

https://www.ninds.nih.gov/
 Thank you for
listening
“In a world where you can be anything,
be kind and understanding to those
facing challenges we may not
comprehend."