Genetic Disorders

The genetic disorders can be divided as:

Type 1. Mendelian Disorders:

These are mainly determined by alteration or mutation in the single gene. These disorders are transmitted in next generation according to the principle of inheritance and can be studied by pedigree analysis. These can be dominant or recessive.

For example, Autosomal dominant disorder are Osteogenesis imperfecta, polycystic kidney disease, Huntington’s Disease, Fatal familial Insomnia, etc. Autosomal recessive disorder are Sickle cell anaemia, cystic fibrosis, xeroderma pigmentosum, Albinism etc.

Some of Mendelian disorders are discussed below:

a. Haemophilia: It is a linked recessive disease, which is transmitted from an unaffected carrier female to some of the male offsprings. Due to this, patient continues bleeding even on a minor injury because of defective blood coagulation. The gene for haemophilia is located on X-chromosome. The defective alleles produce non-functional proteins, which later form a non-functional cascade of proteins involved in blood clotting.

The possibility of a female becoming a haemophilic is extremely rare because mother of such a female has to be at-least carrier and father should be haemophilic. For example, females suffer from this disease only in homozygous condition, i.e., X^CX^C. Queen Victoria was a carrier of haemophilia and produced haemophilic individuals.

b. Colour Blindness: It is a linked recessive disorder, which results in defect in either red or green cone of eye. It does not mean not seeing any colour at all, in-fact it leads to the failure in discrimination between red and green colour. The gene for colour blindness is present on X-chromosome.

It is more present in males (X^CY) because of the presence of only one X-chromosome as compared to two chromosomes in females. A heterozygous female has normal vision, but is a carrier and passes on the disorder to some of her sons. Colour blindness like any other inheritance show crisscross inheritance.

c. Sickle-cell Anaemia: It is an autosome-linked recessive trait that can be transmitted from parents to the offsprings, when both the partners are carrier for the gene (heterozygous).

The disease is controlled by a single pair of allele Hb and Hb . Only the homozygous individuals for Hb^S, i.e., Hb^S Hb^S show the diseased phenotype. The heterozygous individuals are carriers (Hb^A Hb^S).

It is caused by the substitution of glutamic acid (Glu) by valine (Val) at the sixth position of the beta globin chain of the haemoglobin molecule.

The mutant haemoglobin molecule undergoes polymerisation under low oxygen tension causing the change in the shape of the RBC from biconcave disc to the elongated sickle like structure.

d. Thalassemia: It is an autosome-linked recessive disease, which occurs due to either mutation or deletion, resulting in reduced rate of synthesis of one of the globin chains of haemoglobin. Anaemia is the main feature of this disease.

Thalassemia is classified into three types on the basis of globin chain affected:

(i) Alpha (α) Thalassemia: It is controlled by the closely linked genes HBA1 and HBA2 on chromosome 16. In this, the production of globin gene is affected due to the mutation or deletion of one or more of the four alleles.

(ii) Beta (β) Thalassemia: It is controlled by a single gene HBB on chromosome 11. It occurs due to the mutation in one or both the alleles of the gene. Hence, there is a reduced synthesis of beta globin of haemoglobin.

(iii) Delta (δ) Thalassemia: As well as alpha and beta chains present in haemoglobin about 3% of adult haemoglobin is made up of alpha and delta chains. Just like beta thalassemia mutations can occur which affect the ability of this gene to produce delta chains.

e. Phenylketonuria (PKU): It is an inborn error of metabolism, which is inherited as an autosomal recessive trait. It is a rare disease in which baby is born without the ability to properly breakdown an amino acid called phenylalanine.

Babies with this disease have a missing enzyme called phenylalanine hydroxylase, which is needed to break down an essential amino acid phenylalanine into tyrosine in liver. This phenylalanine is accumulated and gets converted into phenyl pyruvic acid and other derivatives leading to mental retardation.

Type # 2. Chromosomal Disorders:

These are caused by the absence or excess or abnormal arrangement of one more chromosomes. The examples are given below:

a. Down’s Syndrome: It was described by J Langdon Down in 1866. It occurs due to the additional copy of chromosome number 21 or trisomy of chromosome 21 in humans and also seen in chimpanzees and other related primates.

Symptoms:

i. Individuals are short statured with small, round head and furrowed tongue.

ii. Partially open mouth, palm is broad with characteristic palm crease.

iii. Slow mental development.

b. Klinefelter’s Syndrome: It occurs due to the presence of an additional copy of X-chromosome resulting in the karyotype 45 + XXY which results into 47 chromosomes.

Symptoms:

i. Individuals have masculine development but feminine characters like development of chest, (gynaecomastia) etc.

ii. Poor bread growth and often sterile and feminine pitched voice.

c. Turner’s Syndrome: It is a disorder caused due to the absence of one of the X-chromosome, i.e., 45 with XO.

Symptoms:

i. Affected females are sterile as ovaries are rudimentary.

ii. Lack of secondary characters and poor chest development. Short stature, small uterus, puffy fingers and webbed neck.

iii. The chromosomal disorders can be studied by the analysis of karyotypes.