Pattern Recognition

• 遺傳分子紀錄著生物體的結構 (genotype)，在遇到不同的環境下控制生物體運行的法則 (phenotype)。

Inherited disease and changes in DNA

• Based on central dogma in molecular biology, DNAs are transcribed to RNAs and then RNAs are translated to proteins. The sequence of DNA determines the sequence of amino acids, and the amino acid sequence determines functions of protein. The relationships between DNA sequences and protein functions are demonstrated by a number of experiments carried out in molecular and biological lab.

• The above procedure is everywhere in nature. Based on the currently medical knowledge, we know lots of examples of naturally occurring changes in DNA that may effect the function on its corresponding protein. Such changes may give rise to disease. Before discussing further more about the disease, it is necessary to classify DNA alterations at first :

  1. First, there are highly local changes, such as point mutations(deletion/insertion/substitution) of a smaller number of nucleotides.
  2. Second, there are large-scale rearrangements of DNA sequences that result from DNA recombination events.

• There are many operations in DNA element operations.

  1. DNA recombination is a process that one portion of DNA moves to another DNA molecule. This may happen during crossing-over.
  2. During DNA trans-location , parts of chromosomes are moved between non-homologous chromosomes.
  3. The third DNA recombination is gene amplification , one region of a chromosome is produced for many copies.

Example.1 : sickle-cell anaemia

• The highly local changes in DNA, such as point mutations, may cause many kinds of disease, for example, sickle-cell anaemia. Sickle-cell anaemia results from changes in polypeptide chains, beta-subunit of haemoglobin. The naming of the disease is due to its abnormal shape of red blood cell observed in people. The shape of whole red blood cell is usually like a sickle. The above reason results in insufficient carrying capability of the oxygen in the blood. The disease may cause pain in different parts of the body, and is life-threatening.

• The causing of sickle-cell aneamia was discovered in 1956.[1-3] Vernon Ingram demonstrated that the amino acid glutamic acid, normally present is position 7 of beta-globin chain, had been changed to valine . This residue is located on the surface of the globin molecule and the mutation forms a hydropoblic state. This mutation makes globin chain aggregate.
  
  

  1. N-terminal part of beta-globin chain.
  2. The mutation in amino acid level is at 7 position, from glutamic acid(GAG) to valine(GUG).
  3. This mutation to valine is much hydrophobic than glutmaic acid, and causes aggregation of haemoglobin molecules.

• Humans have two copies of each chromosome. In case of sickle-cell anaemia, both copies of beta-globin gene are mutated, whereas individuals with one normal gene and one mutated gene are more or less healthy. In the world a part of population that carries the sickle-cell gene is quite large. Why is that? Nature selection does this. The sickle-cell gene protects against malaria because that the responsible parasite, Plasmodium falciparum, lives for a short time in red blood cycle .

Example 2 : Lesch-Nyhan syndrome

• Lesch-Nyhan syndrome is a disease with neurological symptoms in which affected individuals are often characterized by bizarre behaviour such as self-mutilation[4,5]. This disease results from mutations of a gene coding hypoxthanine-guanine phosphoribosyltransferase(HGPRT). This enzyme is involved in the pathway from a purine to its corresponding nucleotides . In the absence of HGPRT, an excess of purines could accumulate overproduction of uric acid. Until now there is no complete explanation for the abnormal actions of LNS. This disease is relatively rare than sickle-cell anaemin, with approximately 1 in 380000 live births affected. LNS may result from a variety of changes, including deletions, insertions and point mutations in CDS, etc.