FROM CHROMOSOMES TO PROTEINS

After DNA synthesis…

There are occasional mistakes during the process of replication, including deletion and duplication.

If not corrected, these can lead to cancer and other genetic disorders (Fanconi Anemia)

Genetic Disorders​ – diseases caused by an abnormality in an individual’s DNA.

Human Genome

46​ Chromosomes

- 23 pairs: 22 pairs autosomal chromosomes or autosomes

: 1 pair sex chromosome

Male ​– x
​ ,y

Female ​– ​x, x

Chromosomal Abnormalities

A. Deletion​ – ​is a missing part of the genetic material, may range in size, from few bases 
to large expanses of the chromosomes 

Ex.​ Cri-du-chat syndrome which is caused by deletion of part of the short arm of
chromosome 5

The regions responsible for the catlike cry is distinct from the region that cause mental
retardation and developmental delay

B. Duplication​ – ​regions of a chromosome where genes are repeated. 

C. Duplication have very important role in ​evolution 

Translocation

Different chromosomes exchange or combine parts.

It can be inherited because they can be present in carriers, who have the normal amount of genetic
material, but rearranged.

 
 

Two Types:

Robertsonian Translocation

o A type of reciprocal translation wherein the short arms of two different acrocentric 
chromosomes break, leaving sticky ends that cause the two long arms to join, forming 
a single, large chromosome with 2 long arms.

o The tiny short arms are lost (or joined), but they contain nonessential sequences and 
eventually got loss during cell division

o Translocation carrier may have 45 chromosomes may not have symptoms if no crucial 
genes have been deleted or damaged.

o Rare form of chromosomal rearrangement that in humans occurs in the five 

acrocentric chromosome pairs, namely 13, 14, 15, 21, and 22

o Also called ​whole-arm translocations​ or ​centric-fusion translocations 

o Chromosome ​21​ and ​14​: heterozygous carrier will be phenotypically normal but 
offspring may have ​Trisomy 21 

Reciprocal Translocation

o Two non-homologous chromosomes exchange parts. But if the chromosome exchange 

does not break any genes, then a person who has both translocated chromosomes is 
healthy and a translocated carrier.

o Affected individuals may produce a characteristics face, absence of bile ducts in the 
liver, abnormalities in the eyes and ribs, heart, and severe itching.

o Symptoms are so variable that carriers do not know they have it

Inversion

o An inverted sequence of chromosome bands indicates that part of the chromosome as 
flipped.

o Inversions usually do not cause any abnormalities in carriers as long as the 

reaarangement is balanced with no extra or missing DNA

o Two Types:

- Paracentric Inversion​ (do not include the centromere)

- Pericentric​ (includes the centromere within the loop)

 
 

Isochromosomes

o A chromosome that has lost one of its arms and replaced it with an exact copy of the 
other arm

o This is sometimes seen in some females with ​turner syndrome​ or in tumor cells. This 
may also cause an isochromosome to have two centromeres

o 20% of the turner​’s​ syndrome results from having 1 normal X and another X which is an 
isochromosome for the long arm

 
 

Ring Chromosome

o Both ends of the chromosome must usually be lost, enabling the arms to fuse together

o However, ring formation can also occur with only end being lost

o Human genetic disorders can be caused by spontaneous ring chromosome formation; 

although ring chromosomes are very rare, they have been found in nearly all human 
chromosomes

o Chromosome 21​: Epilepsy

o Chromosome 14 & 13​: mental retardation

o Chromosome 15​: Dwarfism and microcephaly

Amniocentesis​ (chorionic villus sampling)

o Medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal 

infections and also used for sex determination

o Accuracy of amniocenteesis is about 99.4%

o Involves drawing out the amniotic fluid surrounding the fetus through a small incision 
made on the mother​’​s navel

o Collected fluid contains cells from the fetus that can be analyzed

o Between 16-22 weeks of pregnancy

▪ The cells are grown in a culture medium, then fixed and stained 

▪ Under a microscope the chromosomes are examined for abnormalities. 

▪ The most common abnormalities detected are: 

➢ Down syndrome (trisomy 21)

➢ Edward​’​s syndrome (trisomy 18 [only for male])

➢ Turner​’​s syndrome (monosomy X)

➢ In regard to the fetus, the puncture heals and the amniotic sac replenishes the 
liquid over the next 24-48 hours

Complication of Amniocentesis

▪ Pre-term labor and delivery

▪ Respiratory distress

▪ Postural deformities

 
 

▪ Fetal trauma and alloimmunisation of the mother (​rhesus disease​ – ​during birth, the 
mother may be exposed to the infant​’​s blood, and this causes the development of 
antibodies, which may affect the health of subsequent Rh+ pregnancies).

 
 

Mutations

o Gene mutations can be either inherited from a parent or acquired.

o A hereditary mutation is a mistake that is present in the DNA of virtually all body cells.

o Also called ​germ line​ mutations because the gene change exists in the reproductive 
cells and can be passed from generation to generation, from parent to newborn. 

o Mutation is copied every time body cells divide.

o Mutations occur all the time in every cell in the body.

o Each cell, however, has the remarkable ability to recognize mistakes and fix them 
before it passes them along to its descendants.

o But a cell​’​s DNA repair mechanisms can fail, or be overwhelmed, or become less 
efficient with age. Over time, mistakes can accumulate

Down’s Syndrome

o Caused by non-disjunction of the 21​st​ chromosome.

o This means that the individual has a trisomy (3 ​– ​21​st​ chromosomes)

People with Down syndrome have very distinct facial features: a flat face, a small broad nose, 
abnormally shaped ear, a large tongue, and upward slanting eyes with small folds of skin in 
the corners

Symptoms of Down Syndrome

o Upward slant to eyes

o Small ears that fold over at the top 

o Small, flattened nose

o Small mouth, making tongue appear large

o Short neck

o Small hands with short fingers

o Low muscle tone

o Single deep crease across center of palm

o Looseness of joints

o Small skin folds at the inner corners of the eyes

o Excessive space between first and second toe

 
 

o In addition, down syndrome always involves some degree of mental retardation, from 
mild to severe. In most cases, the mental retardation is mild

 
 

Kleinfelter’s Syndrome

o Disorder occurring due to nondisjunction of the X chromosome

o The sperm containing both X and Y combines with an egg containing the X, results in a 
male child

o The egg may contribute the extra X chromosome

XXY

o Males with some development of breast tissue normally seen in females

o Little body hair is present, and such person are typically tall, have small testes

o Infertility results from absent sperm

o Evidence of mental retardation may or may not be present

Turner’s Syndrome

o Turner syndrome is associated with underdeveloped ovaries, short stature, webbed, 

and is only in women

o Bull neck, and broad chest. Individuals are sterile and lack expected secondary sexual 
characteristics

o Mental retardation typically not evident

o Chromosomal or monogenic