(a) Sickle cell anaemia (an excellent example of single mutation) Sickle cell anaemia is a blood disease (affecting black Africans) where the red blood cells become sickle shaped as compared to normal one.
The sickle cells are rigid & exhibit a higher viscosity to flow causing them to lodge in capillaries. Sickle cell anaemia occurs due to inheritance of a defective allele coding for ?-globin.
It results in the transformation of Hb- A into Hb-S in which glutamic acid is replaced by valine at sixth position in each of two ? -chains of haemoglobin. The major characteristics of this disease are anaemia & a tendency of the red blood cells to change shape at low oxygen concentration.
Due to being insoluble in deoxygenated state sickle cell haemoglobin precipitate in the red blood cells and giving their characteristic bizzare shape.
These cells are useless, so they have to break down & tend to clog in capillaries and small blood vessels & prevent normal blood flow.
II. Disorders of Defective Autosomal Dominant Gene
It is caused by a dominant gene mutation on short arm of 4th chromosome. Its main symptoms are abnormal speech & respiration, and irregular movements of limbs etc. due to atrophy of brain parts. This disease does not appear till the age of 25 to 35.
This is the most common kind of short limbed dwarfism due to cartilage formation. Intellect (IQ) is not affected.
Diseases of more than five digits in fingers & toes and small sized fingers respectively
This disease is due to dominant mutation resulting in the production of abnormal form of connective tissues and characteristic extreme looseness of joints.
The long bones of body grow longer; fingers are very long called ‘spider fingers’ or arachnodactyly; weakness develops in the connective tissue and lenses in eyes become displaced.
The diagnosis is made on clinical grounds, with involvement in at least two body systems. The molecular basis of Marfan syndrome is mutation of a structural gene (related to fibrillin protein) on chromosome 15.
It is the most common diseases in North America, rare in Asia including India; the body produces abnormal glycoprotein which interferes with salt metabolism.
The sweat in body becomes rich in sodium chloride; the mucous secreted by body becomes abnormally viscid which blocks passages in the lungs, liver and pancreas. Due to defective liver functioning the fat digestion will not be normal. One of the principal organs affected by cystic fibrosis is pancreas which develops fibrous growth.
The gene, responsible for this defect, has been localized to chromosome 7 and it codes for a chloride transport factor (CFTR) and multiple alleles.
III. Disorders of Recessive Sex-Linked Gene:
Haemophilia is also known as bleeder disease (John Otto, 1803). It is a popular example of sex-linked inheritance in human beings. It occurs due to deficiency of plasma thromboplastin (haemophilia, Christmas disease) or antihaemophilia globulin (haemophilia A) during which the exposed blood does not clot. Haemophilia appears only in human male which can be transferred to their grandson through his carrier daughter (criss-cross inheritance). Homozygous condition is lethal.
Muscular dystrophy occurs due to non-synthesis of protein, dystrophin which is required for transfer of nerve impulse to calcium storing regions of the muscle. Muscular dystrophy is of two types – Duchenne’s pseudohypertrophy and Becker’s/benign pseudohypertrophic dystrophy (less severe). It is characterised by deterioration of muscles at an early age with progressive weakness of girdle muscles, inability to walk after age of 12, cardiomyopathy and mental impairment.
G-6-PD deficiency syndrome occurs due to deficiency of glucose 6-phosphate dehydrogenase (essential for carrying out hexose monophosphate shunt). In the absence of G-6-PD, haemoglobin crystallises and erythrocyte membrane ruptures during oxidant stress.
Congenital night blindness causes reduced development of visual pigment (rhodopsin) that interferes with the function of retinal rods. This night blindness is sex-linked inheritance which is caused by a recessive gene carried by X-chromosome. It also occurs due to vitamin A deficiency which is a type of acquired night blindness.
A particular trait in human beings renders them unable to differentiate between red colour and green colour, hence also called red-green colourblindness. The gene for this red green colour blindness is located on X-chromosome. Colourblindness is recessive to normal vision so that if colour blind man marries a girl who is normal (homozygous) for this character, sons will be normal, but daughters will be heterozygous (normal phenotype), which means that these daughters would be carriers of this trait. If such a carrier girl marries a colourblind man, 50% female progeny and 50% of male progeny would be colourblind.
Red green colour blindness is also called daltonism or proton defect. Colourblindness is of three types: protanopia (red colour blindness), deuteranopia (green colour blindness) & tritanopia (blue colour blindness). It shows criss-cross inheritance as in haemophilia.