Biology MENDELIAN DISORDERS

### KEY TOPICS

star Mendelian Disorders
star Hemophilia
star Sickle cell Anaemia
star Phenylketonuria

### MENDELIAN DISORDERS

● Broadly, color{Violet}"genetic disorders" may be grouped into two categories – color{Violet}"Mendelian disorders" and color{Violet}"Chromosomal disorders".

● Mendelian disorders are mainly determined by color{Violet}"alteration or mutation" in the color{Violet}"single gene".

● These disorders are transmitted to the offspring on the same lines as we have studied in the color{Violet}"principle of inheritance".

● The color{Violet}"pattern of inheritance" of such Mendelian disorders can be traced in a family by the color{Violet}"pedigree analysis".

● Most common and prevalent Mendelian disorders are color{Violet}"Haemophilia", color{Violet}"Cystic fibrosis", color{Violet}"Sickle-cell anaemia", color{Violet}"Colour blindness", color{Violet}"Phenylketonuria", color{Violet}"Thalesemia", etc.

● It is important to mention here that such Mendelian disorders may be color{Violet}"dominant or recessive".

● By color{Violet}"pedigree analysis" one can easily understand whether the trait in question is dominant or recessive.

● Similarly, the trait may also be linked to the color{Violet}"sex chromosome" as in case of haemophilia.

● It is evident that this color{Violet}"X-linked recessive trait" shows transmission from color{Violet}"carrier female" to male progeny.

### HAEMOPHILIA

● This color{Violet}"sex linked recessive" disease, which shows its transmission from color{Violet}"unaffected carrier female" to some of the color{Violet}"male progeny" has been widely studied.

● In this disease, a single protein that is a part of the cascade of proteins involved in the color{Violet}"clotting of blood" is affected.

● Due to this, in an affected individual a color{Violet}"simple cut" will result in color{Violet}"non-stop bleeding".

● The color{Violet}"heterozygous female" (color{Violet}"carrier") for haemophilia may transmit the disease to color{Violet}"sons".

● The possibility of a color{Violet}"female" becoming a color{Violet}"haemophilic" is extremely color{Violet}"rare" because mother of such a female has to be at least carrier and the father should be haemophilic (unviable in the later stage of life).

● The family pedigree of color{Violet}"Queen Victoria" shows a number of color{Violet}"haemophilic descendents" as she was a carrier of the disease.

### SICKLE-CELL ANAEMIA

● This is an color{Violet}"autosome linked recessive" trait that can be transmitted from parents to the offspring when color{Violet}"both the partners" are carrier for the gene (or heterozygous).

● The disease is controlled by a single pair of allele, color{Violet}"HbA and HbS".

● Out of the three possible genotypes only homozygous individuals for color{Violet}"HbS (HbS HbS)" show the color{Violet}"diseased phenotype".

● color{Violet}"Heterozygous (HbAHbS)" individuals appear apparently unaffected but they are color{Violet}"carrier of the disease" as there is 50 per cent probability of transmission of the mutant gene to the progeny, thus exhibiting sickle-cell trait

● The defect is caused by the substitution of color{Violet}"Glutamic acid" (Glu) by color{Violet}"Valine" (Val) at the color{Violet}"sixth" position of the color{Violet}"beta globin chain" of the color{Violet}"haemoglobin" molecule.

● The substitution of amino acid in the globin protein results due to the color{Violet}"single base substitution" at the sixth codon of the beta globin gene from color{Violet}"GAG to GUG".

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

### PHENYLKETONURIA

● This color{Violet}"inborn error of metabolism" is also inherited as the color{Violet}"autosomal recessive" trait.

● The affected individual lacks an color{Violet}"enzyme" that converts the amino acid color{Violet}"phenylalanine into tyrosine".

● As a result of this phenylalanine is color{Violet}"accumulated" and converted into color{Violet}"phenylpyruvic acid" and other derivatives.

● Accumulation of these in color{Violet}"brain" results in color{Violet}"mental retardation".

● These are also excreted through color{Violet}"urine" because of its color{Violet}"poor absorption" by kidney.