`star` Mendelian Disorders
`star` Hemophilia
`star` Sickle cell Anaemia
`star` Phenylketonuria


● 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.


● 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.


● 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.


● 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.