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Genetic Disorders

Original Editor - Dr. Elaine Lonnemann Top Contributors - Rana Muhammad Tahir Aslam, Kim Jackson, Elaine Lonnemann and Admin

This article is currently under review and may not be up to date. Please come back soon to see the finished work! (19/09/2024)

Introduction

A gene is the structural and functional unit of the inheritance.Gene is responsible for the transmission of traits (eye colour, height and many more) from the parents to the children.A gene is sequence of DNA that present in the nucleus of the cell and is located at specific locations on the Chromosomes.[1] Molecularly a sequence of base pairs that made up the DNA and produce functional products like RNA & Peptides when decoded is known as the Gene. [2] Gene encodes Gene products that are proteins and not to mention the non-coding RNA molecules (ncRNAs). These proteins and non-coding RNAs are then responsible for the molecular functions and cellular components.[3] Many molecular functions collectively give rise to biological processes that are responsible for the normal functioning of a human being. According to a research performed in 2004, the human genome codes for 20,000-25,000 protein coding genes.[4]

Any change that alter the genetic information on a gene, like change in the DNA sequence, or any damage to the DNA or Chromosome, could lead to change in the biological processes and hence pathologies.[2]Hence any disorder arising in a newborn or adult that is due to any kind of defected gene would be classified as a genetic disorder.

Types of Genetic Disorders

On the basis of Level of the Damage or Mutation, Genetic disorders can be grouped into three main categories.But in order to understand the types we have to get familiar with some common terms & concepts as follow.

  1. There are 46 number of chromosomes (haploid) in a normal human being that it inherit from the it parents.
  2. out of 46 number of chromosomes, 23 number of chromosomes(diploid) are inherited from mother and 23 number of chromosomes are inherited from the father side.
  3. In diploid number of chromosomes, the last 23rd chromosome is the sex chromosome that specify the gender of the person. It can either be X or Y chromosome.Remaining 22 chromosomes are known Autosomes[2]
  4. A gene is present on a specific location on a chromosome, that location is known as the locus, on which a allele is positioned.
  5. A diploid chromosome have two alleles of a gene.[2]
  6. When a gene is expressed, it forms RNA that RNA is then serve as a template to produce Proteins that in turn produce biological actions.[5]

For detailed concept of gene expression watch this video

Single Gene Disorders

Single Gene Disorders are also known as the Mendelian Disorders. Any disease arising from the damage to a gene, that can be due to change or mutation in the DNA sequence of a gene or due to error in the base pairs of DNA is regarded as the Single Gene Disorder.[6] You must not confuse the polymorphic changes in the genetic material with the Single Gene Disorders. Polymorphic are variations of the variations of the genetic material but unlike the Mutations in the Single Gene Disorders they do not cause the pathologies. But these polymorphic changes in the genetic material increase the chances of pathologies.[7]The single gene disorders are divided into Autosomal Dominant, Autosomal Recessive, X-linked Recessive and X-linked Dominant Disorders.[2]

  • Autosomal Dominant Disorder: In autosomal dominant disorders, only one allele of the gene pair needs to be affected to cause the disease. Autosomal refers to the fact that it affect only autosomes and both genders at equal risks. In this affected gene can be either from maternal or from paternal side. Parents have 50% chances to transmitting the disease to the child. [8] Some of the Autosomal Dominant Disorders are achondroplasia (due to mutation in FGFR3 gene[9]) Marfan syndrome, Neurofibromatosis and Tuber sclerosis.[8]
  • Autosomal Recessive Disorder: In autosomal dominant disorders, both of the gene are mutated and together they cause the disease. This Disease also affect both genders equally. In autosomal recessive disorders, one mutated gene is from the mother side and other is from father side. Parents have 25% chance of transmitting the disease to the child.[8] Some of the Autosomal recessive disorders are sickle cell anaemia (due to mutation in HBB gene encoding for beta chain[10]), phenylketonuria, cystic fibrosis and Homocystinuria.
  • X-linked Recessive Disorder: when both of the gene pair present on the x chromosomes are mutated or damaged, they lead to the X-linked recessive disorders. A X-linked recessive disorder is carried by females but it affects the males. Fathers can not transmit the disease to their son.[2] The perfect example of this is Duchenne Muscular Dystrophy and Haemophilia.
  • X-linked Dominant Disorder: when one of the gene pair present on the x chromosomes are mutated or damaged, that lead to the X-linked recessive disorders. This disorder mostly affects the females rather than males. There is no Male to Male transfer of the affected genes.[2] Example of X-linked dominant disorders are Rett syndrome & Hypophosphatemia.

Chromosome Disorders

Multifactorial Disorders

References

  1. ↑ National Cancer Institute. NCI Dictionary of Genetics Terms. Available from: https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/gene
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Mahdieh N, Rabbani B. An overview of mutation detection methods in genetic disorders. Iran J Pediatrics. 2013 Aug;23
  3. ↑ The Gene Ontology Consortium,The Gene Ontology knowledgebase in 2023, Genetics, Volume 224, Issue 1, May 2023, iyad031, https://academic.oup.com/genetics
  4. ↑ International Human Genome Sequencing Consortium (2004). Finishing the euchromatic sequence of the human genome. https://www.nature.com/articles
  5. ↑ Passmore, L.A., Coller, J. Roles of mRNA poly(A) tails in regulation of eukaryotic gene expression. Nat Rev Mol Cell Biol (2022). https://www.nature.com/articles
  6. ↑ Epedia Difference Between Genetic and Hereditary Diseases Available from: https://pediaa.com/difference-between-genetic-and-hereditary-diseases/
  7. ↑ Milewicz, D.M. (2007). Classification of Genetic Disorders. In: Willerson, J.T., Wellens, H.J.J., Cohn, J.N., Holmes, D.R. (eds) Cardiovascular Medicine. Springer, London. https://link.springer.com/chapter/10
  8. ↑ 8.0 8.1 8.2 Shen Gu, Bo Yuan, Ethylin Wang Jabs, Christine M. Eng, Chapter 2 - Basic Principles of Genetics and Genomics, Editor(s): Antonie D. Kline, Ethylin Wang Jabs,Genomics in the Clinic, Academic Press, (2024), Pages 5-28, https://www.sciencedirect.com/science/article
  9. ↑ Richette, P., Bardin, T., & Stheneur, C. (2008). Achondroplasia: from genotype to phenotype. Joint bone spine. https://www.sciencedirect.com/science
  10. ↑ Steinberg M. H. (2008). Sickle cell anemia, the first molecular disease: overview of molecular etiology, pathophysiology, and therapeutic approaches. TheScientificWorldJournal, 8, 1295–1324. https://onlinelibrary.wiley.com
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