ANA 231-ANOMALIES OF AUTOSOMAL AND SEX CHROMOSOMES, GENE MUTATION AND DISEASES.

Chromosomes are made up of complex substance called nucleic acid. Each chromosome is divided
into units called genes which carry hereditary materials. The total number of chromosome per cell
is constant. Man has 46 chromosomes per cell except the gametes which has 23single
chromosomes. The 46 chromosomes are made up of 44 autosomes and 2 sex chromosomes.

Chromosome is made of long strands of DNA and contains many genes. The genes are arranged in a
particular sequence and each has a particular location on the chromosome called its locus.

Chromosome Anomalies

Chromosome anomalies are disorders in the genome. They occur due to error in cell division or
mutation(changes in the structure of DNA). The former is heritable but the later is non heritable.
They occur as accident in the egg or spermatozoon.

Factors responsible for chromosomal anomalies

 Error in cell division- Non disjunction

 Mutation-structural change
 Age- older women at high risk of giving birth to babies with anomalies.
 Environment- pollutant exposure
 Lifestyle

Anomalies can be numerical or structural . Neumerical anomaly is called Aneuploidy. This could
be either missing chromosome from a pair (monosamy) or has more than 2 of a pair(trisomy).
Eg Down’s syndrome (Trisomy 21 ) and Turner’s syndrome (monosamy with only one sex
chromosome.

Types of structural Alterations:

Deletion, Duplication, Translocation,reciprocal translocation, Robertbesonian translocation,

inversion, insertion, rings, isochrome.

AUTOSOMAL ANOMALIES

1. Down’s syndrome (Trisomy 21). Caused by meotic non disjunction. The chromosomes
can not pair back after separating to divide. This gives rise to an extra chromosome in
the number 21 pair. Mutation can also cause it. Some could be mosaic- not all the cells
are abnormal.

Features: Single palm crease called Simian crease, broad short head with low set ears, moon
face, mental retardation, protruding tongue, poor moto skills, speech disorder, short and
stout and others. Condition can be diagnosed prenatally with amniocentesis. Females who
have given birth to baby with trisomy are advised to undergo amniocentesis.

2. Trisomy 22(DiGeorge syndrome). Also called craniofacial syndrome. Caused by deletion

of the long arm of chromosome number 22.
 Features-heart defects, impaired immune system because of thymic hyperplasia with T-cell
immunity defect and developmental delays eg Palatal anomalies, congenital heart disease,
facial dysmorphia-eyes, ears, nose look abnormal, microcephaly. Most babies with this die
during development and usually not born.

3. Trisomy18-Edwards syndrome: Extra chromosome at number 18 chromosome. Affected

individuals die during prenatal stage. Features- Those who survive have short neck,
micognathia(small head) congenital heart defect, renal malformation, look weak and
fragile incidence is 1:8000. Boys are more affected.
4. Trisomy 13 Batholin-patau syndrome: Extra chromosome at N0. 13 chromosome.
Features- heart defects,brain or spinal cord anomalies, microphthalmia(small eyes),
cleft lip, extra fingers or toes(polydactyly), occurs in 1;10,000 new borns. Incidence is
higher in females.
5. Cri-du-chat syndrome: Caused by deletion on the short arm of chromosome 5. Multiple
genes are missing because of this deletion eg TERT (Telomerase reverse transcriptase).
The larynx develops poorly causing the child to cry like a cat. Features: small head, cry
like a cat. Widely set eyes, fold of skin over the eyes, unusually round face.
6. William’s syndrome- Missing genetic material at chromosome 7 including the gene ,
elastin . Features- disorders of the circulatory system and the heart.

Single gene disorder is the result of a single mutated gene. Over 4000 human diseases are
caused by single gene defect

SEX CHROMOSOME ANOMALIES

These are less common. Can be diagnosed before birth by amniocentesis and chorionic villi
sampling. Sex chromosome anomalies are gender specific. Female anomalies are due to
variations in X chromosome, male anomalies are due to variations in either X or Y
chromosome or both. Among others include-

1. Turner’s syndrome- females inherit only one chromosome, their genotype is

XO(monosomy X). Usually females. Features- If they survive-short adults, werbed
neck,small jaws,exceptionally small widely spaced breast. 1;2000 or 5000
2. Triple-X- syndrome- have genotype XXX. Are called super females, usually taller than
average with long legs and slender toes, have learning difficulties
3. Klinefelters syndrome-males inherit extra x chromosome and so have XXY. Have
high pitched voice, breast enlargement, learning difficulties as children especially
with language and have short term memory.
4. XYY syndrome- supermales. Also called Jacobs syndrome, male inherit extra Y
chromosome hence have XYY. Are tall and slender, facial Acne, poorly
coordinated.1:900 male births.

PATTERN OF INHERITANCE

 Autosomal dominant- only one mutated copy of the gene is necessary for a person to
be affected by this disorder the affected usually has one affected parent. The chance is
 50%. Not all who inherit it go on to develop the disease. Examples of this disorder
are, Hutington’s disease, hereditary non polyposis colorectal cancer
 Autosomal recessive-Two copies of the gene must be mutated for a person to be
affected. Affected person usually has unaffected parents who carry each a single copy
of the mutated gene and is called ‘a carrier’. Eg Cystic fibrosis, sickle cell disease.
 X -linked Dominant: Caused by mutations in genes on the X chromosome. Males and
female are affected. The sons of a man with an x linked dominant disorder will not be
affected. A woman with an X linked disorder has a 50% chance of having an affected
fetus with each pregnancy. Eg Rett syndrome
 X -liked recessive: Caused by mutations in genes on the x chromosome. The sons of a
man with this disorder will not be affected but the daughters will carry a copy of the
gene. A woman who is a carrier of this disorder has 50% chance of having sons
affected and 50% chances of the daughters carrying a copy of the mutated gene and
are therefore carriers. Eg are Haemophilia A, Colour blindness, male pattern baldness
 Y-linked diseases: Caused by mutations on the Y chromosomes. Only passed to the
sons, females not affected. Y linked disorders are rare, the ones known cause
infertility.
 Mitochondrial disease: Applies to genes in mitochondrial DNA. Only eggs contribute
mitochondria to the developing embryo, so only mothers can pass on the disorder. Eg
is hereditary optic neuropathy.

MUTATION
Mutation is a permanent change in the genetic material DNA. Those that affect germ
cells may be transferred to the progeny. Those in the somatic cells may not be
transferable but contribute to congenital diseases.
CAUSES OF MUTATION
Chemicals, nitrous acid, alkylating agents, bromouracil, antiviral drug, benzpyrene in
tobacco smoke, xrays, ultraviolet light, certain viruses.

TYPES OF MUTATTION
1. Point mutation:- Change in a single base pair. There is substitution of a single
nucleotide base by a different base. This is divided into:
a. Mis sensene mutation: This results in a protein in which one amino
acid is substituted for another.
b. Non sense mutation: This results in a protein in which a stop codon
replaces an amino acid codon leading to premature termination of
translation.
c. Frameshift mutation: Insertion or deletion of one or two base pairs,
alters the reading frame of the DNA strand leading to introduction of
unrelated amino acid into the protein generally followed by a stop
codon.
d. Silent mutation: This results in a protein in which the same amino
acid is coded again.
2. The second major type involves large scale changes in chromosome
structure. This can affect the functioning of numerous genes resulting in
major phenotypic consequences.
Mutation can lead to abnormal chromosome number, structure, DNA
sequence changes in specific genes. Mutations can occur spontaneously or be
induced. Many diseases with devastating effects are results of mutation,eg
Sickle cell anaemia is caused by a missense mutation at codon 6 of the beta
globin gene. As a result the glutamic acid at position 6 in the normal protein is
changed to a valine in the mutant protein. This alteration adversely affects
haemoglobin.