Anggelia Puspasari

Biochemistry Departement
Faculty of Medicine and Health Sciences
Universitas Jambi
 Describe chromosomal diseases
 Describe single gene disorders and it hereditary principal
 Describe multifactorial diseases and how its affect the diseases
 Describe mitochondrial diseases
 Chromosomes are made up of tightly packed lengths of DeoxyriboNucleic Acid (DNA).
 Human have 22 pairs autosome and one pair sex chromosome.
 Genes are specific lengths of DNA that determine the order of amino acids used to make
protein. A gene is the basic physical and functional unit of heredity.
 In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases.
Humans have between 20,000 and 25,000 genes.
 Alleles are forms of the same gene with small differences in their sequence of DNA bases.
These small differences contribute to each person’s unique physical features.
 Dysfunctional gene behaviour is commonly termed as a mutation. These mutations
are responsible for causing illnesses.
 According to the degree of gene mutation, diseases are categorised into the following:
1.Chromosomal diseases: occur when the entire chromosome, or large segments of a
chromosome, is missing, duplicated or otherwise altered. Down Syndrome is a
prominent example of a chromosomal abnormality.
2.Single-gene disorders: occur when an alteration occurs in a gene causing one gene to
stop working. An example of a single gene disorder is sickle-cell anaemia.
3.Multifactorial disorders: occur as the result of mutations in multiple genes, frequently
coupled with environmental causes. An example of a multifactorial disorder is
diabetes.
4.Mitochondrial disorders: are rare disorders caused by mutations in non-chromosomal
DNA located within the mitochondria. (The mitochondria are subcellular organelles.)
These disorders can be found to affect any part of the body including the brain and
the muscles
 Classified into two main types; numerical and structural disorders.
 Examples of numerical disorders include trisomy, monosomy and triploidy. Down
syndrome (trisomy 21), trisomy 13, trisomy 18, Klinefelter syndrome and Turner
syndrome.
 Structural chromosome disorders result from breakages within a chromosome. In
these types of disorders there may be more or less than two copies of any gene.
• Chromosomal deletions, sometimes known as partial monosomies, occur when a piece or
section of chromosomal material is missing. Example: cri-du-chat syndrome and 22q11.2
deletion syndrome.
 Chromosomal duplications, sometimes known as partial trisomies, occur when there is an
extra copy of a segment of a chromosome. Example: MECP2 duplication syndrome
 Unbalanced translocations occur when a chromosome segment is moved from one
chromosome another.
 Inversions occur when a chromosome breaks in two places and the resulting piece of DNA is
reversed and re-inserted into the chromosome.
 Isochromosomes are abnormal chromosomes with identical arms - either two short (p) arms
or two long (q) arms
 Dicentric chromosomes result from the abnormal fusion of two chromosome pieces, each of
which includes a centromere.
 Ring chromosomes form when the ends of both arms of the same chromosome are deleted,
which causes the remaining broken ends of the chromosome to be "sticky"

 Single gene disorders are caused by DNA changes in one particular gene, and often
have predictable inheritance patterns.
 Individually, single gene disorders are each very rare, but as a whole, they affect about
one per cent of the population.
 Single gene disorders can be divided into different categories: dominant, recessive
and X-linked
 Dominant diseases are single gene disorders that occur in the
heterozygous state when an individual has one mutant copy of the
relevant gene and one healthy copy.
 The effects of the mutant version of the gene (allele) override the
effects of the healthy version of the gene. So, the mutant allele causes
disease symptoms even though a healthy allele is present.
 Dominant disorders spread vertically down family trees, from parent to
child.
 In rare cases when an individual has two copies of the mutant gene
(also known as being homozygous the disorder symptoms are generally
more severe.
 An example of a dominant single gene disorder is which is a disease of
the nervous system. Huntington’s disease.
 Recessive diseases are single gene disorders that only occur in the homozygous state
- when an individual carries two mutant versions (alleles) of the relevant gene.
 The effects of the healthy allele can compensate for the effects of the mutant allele.
The mutant allele does not cause disease symptoms when a healthy allele is also
present.
 Recessive diseases are more difficult to trace through family trees because carriers
of a mutant allele do not show symptoms of the disease. It therefore appears that the
disease has skipped a generation when it is seen in groups of children within a family.
 The risk of an individual having a recessive disorder increases when two people who
are closely related have a child together (consanguinity). This is because there is a
much greater chance that the same mutant allele will be present in related parents.
 X-linked disorders are single gene disorders that result from the presence of a
mutated gene on the X chromosome.
 The inheritance patterns of X-linked diseases are simplified by the fact that males
always pass their X chromosome to their daughters but never to their sons.
 Because females (XX) have two copies of the X chromosome but males (XY) only
have one copy, X-linked disorders are more common in males. If a male’s single copy
on the X chromosome is mutated he has no healthy copy to restore healthy function.
 Like other single gene disorders, X-linked disorders can be either recessive or
dominant.
 X-linked recessive disorders are much more common in males than females because two
copies of the mutant allele are required for the disorder to occur in females, while only
one copy is required in males.
 Examples of X-linked recessive disorders include red-green colour blindness, haemophilia
and the Duchenne and Becker forms of muscular dystrophy.
 The overall pattern of the disease is characterised by the transmission of the disease from
a carrier mother, who inherited a copy of the mutant gene from her affected father (this is
sometimes described as a ‘knight’s move’).
 Males always pass their X chromosome to their daughters but never their sons (who
receive their Y chromosome). These daughters are described as obligate carriers.
 Female carriers pass the defective X chromosome to half of their daughters (who are
carriers) and half of their sons (who will be affected by the disease). Their other children
will inherit the healthy copy of the gene.
 Carrier females may show disease symptoms if there is a chromosome disorder or a
problem with X chromosome inactivation.
 X-linked dominant disorders are very uncommon. Examples include Rett syndrome (a
condition found almost exclusively in girls that seriously affects brain development,
causing severe disabilities) and some inherited forms of rickets (slowed growth and
skeletal development due to vitamin D deficiency).
 Unlike X-linked recessive disorders, the frequency of X-linked dominant disorder is
similar in males and females.
 Unlike other dominant diseases, X-linked dominant disorders cannot be transmitted
from father to son because fathers do not pass their X chromosome to their sons
• Multifactorial (complex disorders) : interaction between genetic and
environmental factors
• Fa m i l y m e m be r s h a r e a gr e a t e r pr o po r t i o n o f ge n e t i c s a n d
env iro nmental fac to rs than ind iv id ual in po pulatio ns (familial
aggregation)
• Gene-gene interactions : one is additive for others

• Gene-environment interactions : environment affect gene expression

Qualitative Trait
Absence or presence of disease
Concordant : two individual in a family have the same disease (more
possible that genetic factors contribute for the development of diseases)
E.g. : hypertension, type 2 diabetes
Discordant : only one of a pair in a family has the disease (less possible
that genetic factors contribute)
E.g. : post partum hemorrhage
Quantitative Trait
Measurable physiological quantities : blood pressure, cholesterol level,
BMI
Such variation due to genetic and non-genetic factors.
Individuals with certain genetic variants are susceptible (has risk factor)
E.g. : Angiotensin converting enzyme polymorphism with blood pressure;
ApoE polymorphism with dyslipidemia
Not single gene disorders nor mendelian
Demonstrate familial aggregation
P a i rs o r rel a t i ve m a y s t i l l be di s c o rda n t
because of non-genetic factors
Common among close relative of the patients
 Mitochondrial genetic disorders can be caused by changes (mutations) in either the
mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and
inadequate production of energy.
 Those caused by mutations in mitochondrial DNA are transmitted by maternal
inheritance, while those caused by mutations in nuclear DNA may follow an
autosomal dominant, autosomal recessive, or X-linked pattern of inheritance.
 Conditions resulting from mutations in mitochondrial DNA can appear in every
generation of a family and can affect both males and females
 People with these conditions can present at any age with almost any affected body
system; however, the brain, muscles, heart, liver, nerves, eyes, ears and kidneys are
the organs and tissues most commonly affected. Symptom severity can also vary
widely.
 A woman who have one mutant allele of a diseases married with a man who have
one mutant allele of a diseases. The diseases is single gene disorder. They have two
daughters and two sons. How the probability of their child to get the single gene
disorder? *if the single gene disorder hereditary pattern is
1.Autosomal dominant

2.Autosomal recessive

3.X-linked dominant

4.X-linked recessive
Thank You