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Human genetic disorders
HAMZA ABDULLAH
Department of computational biology and bioinformatics
Abstract
Human is a one of the Almighty’s complex creation. Humans are made up of trillions of cells and these cells holds the DNA which is composed of
hereditary material. Information stored on DNA is transferred from one generation to another. Which transfers unique features from parents
to the next generation and so on. Sometimes DNA has error in its information which cause different problems like genetic diseases. And these
genetic disorders if transferred to the next generation could be an incurable disease. Genetic disorders are of different types i.e. single-gene
disorders, chromosomal disorders, complex disorders. This paper intends to be as an introductory paper for the project “Human genetic
disorders”.
Keywords:
Genetics, genetic disorders, mutation
Introduction
A genetic disorder or a genetic disease is a condition which is caused by the error in someone’s DNA. And these errors in a DNA can be of
different type, either single base mutation, single gene or multiple gene or it can involve the addition or subtraction of entire chromosome
causing the genetic disease. Genetic disorders can be caused by single or multiple errors in an individual’s genome. Which are categorized as
Single gene disorders, Chromosomal disorders or complex disorders.
1.1 Single gene disorders
Single-gene disorders are a type of genetic disorders in which only one or specific gene is mutated. It is sometimes also called as “Mendelien
genetic disorders”. Currently there are about 4000 genetic disorders according to the scientists which are caused by the mutation in one
gene. And some of these genetic diseases can be transferred from parents to the offspring.
Some single gene disorders include
• cystic fibrosis
• sickle cell anemia
• Fragile X syndrome
• muscular dystrophy
• Familial hypercholesterolemia (FH)
Above are the some of the single gene disorders that affects at least 1 in 500 people around the globe.
Table 1: Examples of Human Diseases, Modes of Inheritance, and Associated Genes
Disease
Type of Inheritance
Gene Responsible
Phenylketonuria (PKU)
Autosomal recessive
Phenylalanine hydroxylase (
PAH
)
Cystic fibrosis
Autosomal recessive
Cystic fibrosis conductance transmembrane regulator (
CFTR
)
Sickle-cell anemia
Autosomal recessive
Beta hemoglobin (
HBB
)
Albinism, oculocutaneous, type II
Autosomal recessive
Oculocutaneous albinism II (
OCA2
)
Huntington's disease
Autosomal dominant
Huntingtin (
HTT
)
Myotonic dystrophy type 1
Autosomal dominant
Dystrophia myotonica-protein kinase (
DMPK
)
Hypercholesterolemia, autosomal dominant,
type B
Autosomal dominant
Low-density lipoprotein receptor (
LDLR
); apolipoprotein B (
APOB
)
Neurofibromatosis, type 1
Autosomal dominant
Neurofibromin 1 (NF1)
Polycystic kidney disease 1 and 2
Autosomal dominant
Polycystic kidney disease 1 (
PKD1
) and polycystic kidney disease 2 (
PKD2
), respectively
Hemophilia A
X-linked recessive
Coagulation factor VIII (
F8
)
Muscular dystrophy, Duchenne type
X-linked recessive
Dystrophin (
DMD
)
Hypophosphatemic rickets, X-linked dominant
X-linked dominant
Phosphate-regulating endopeptidase homologue, X-linked (
PHEX
)
Rett's syndrome
X-linked dominant
Methyl-CpG-binding protein 2 (
MECP2
)
Spermatogenic failure, nonobstructive, Y-linked
Y-linked
Ubiquitin-specific peptidase 9Y, Y-linked(
USP9Y
)
1.2 Chromosomal disorders
Chromosomal disorders are another type of genetic disorders which are caused due to an error at chromosomal level. Due to addition or
subtraction of entire gene from the chromosome or because of structural changes in the chromosomes. Down syndrome, for example, is
caused by an extra copy of chromosome 21 (called trisomy 21), although no individual gene on the chromosome is abnormal. Prader-Willi
syndrome, on the other hand, is caused by the absence or non-expression of a group of genes on chromosome 15. A specific form of blood
cancer (chronic myeloid leukemia, CML) may be caused by a chromosomal translocation, in which portions of two chromosomes
(chromosomes 9 and 22) are exchanged. No chromosomal material is gained or lost, but a new, abnormal gene is formed that leads to
formation of cancer.
Chromosomal disorders are further organized into two basic types
• Numerical abnormalities
• Structural errors
Numerical abnormalities are due to the missing of one of the chromosome from the pair, condition called monosomy. Another condition
called trisomy in which more than one chromosome is missing.
Down syndrome is the example of numerical abnormalities in chromosomes.
Whereas the structural errors are due to the change in the structure of a chromosome. Which can be altered in several ways.
• Deletions: A portion of the chromosome is missing or deleted.
• Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material.
• Translocations: A portion of one chromosome is transferred to another chromosome. There are two main types of translocation.
In a reciprocal translocation, segments from two different chromosomes have been exchanged. In a Robertsonian translocation,
an entire chromosome has attached to another at the centromere.
• Inversions: A portion of the chromosome has broken off, turned upside down, and reattached. As a result, the genetic material is
inverted.
• Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss of genetic
material.
Most of the chromosomal disorders occur at conception level when egg and sperm conceived which is why these kinds of abnormalities
occur at every cell level. And it can be transferred to the next generation.
Figure 1: Visualization of a DNA
1.3 Complex disorders
Complex disorders or multifactorial inheritance disorders are also another type of human genetic disorders which are caused due to small
inherited variations in genes and often triggered together with environmental factors causing different type of diseases. i.e. Heart disease,
diabetes, and most cancers are examples of such disorders. Behaviors are also multifactorial, involving multiple genes that are affected
by a variety of other factors. Researchers are learning more about the genetic contribution to behavioral disorders such as alcoholism,
obesity, mental illness and Alzheimer's disease.
List of some genetic disorders
1. Achondroplasia
2. Alpha-1 Antitrypsin Deficiency
3. Antiphospholipid Syndrome
4. Autism
5. Autosomal Dominant Polycystic Kidney Disease
6. Breast cancer
7. Charcot-Marie-Tooth
8. Colon cancer
9. Cri du chat
10. Crohn's Disease
11. Cystic fibrosis
12. Dercum Disease
13. Down Syndrome
14. Duane Syndrome
15. Duchenne Muscular Dystrophy
16. Factor V Leiden Thrombophilia
17. Familial Hypercholesterolemia
18. Familial Mediterranean Fever
19. Fragile X Syndrome
20. Gaucher Disease
21. Hemochromatosis
22. Hemophilia
23. Holoprosencephaly
24. Huntington's disease
25. Klinefelter syndrome
26. Marfan syndrome
27. Myotonic Dystrophy
28. Neurofibromatosis
29. Noonan Syndrome
30. Osteogenesis Imperfecta
31. Parkinson's disease
32. Phenylketonuria
33. Poland Anomaly
34. Porphyria
35. Progeria
36. Prostate Cancer
37. Retinitis Pigmentosa
38. Severe Combined Immunodeficiency (SCID)
39. Sickle cell disease
40. Skin Cancer
41. Spinal Muscular Atrophy
42. Tay-Sachs
43. Thalassemia
44. Trimethylaminuria
45. Turner Syndrome
46. Velocardiofacial Syndrome
47. WAGR Syndrome
48. Wilson Disease
Genetic disorders in Pakistan
Pakistan is a country with 197 million (2017) of population. And most of the marriages trends are within the close family relatives or with in
the first cousin family circle. According to the PGMD website data, the rate of consanguineous marriages (marriages among close cousins)
in Pakistan is 62.70 per cent — by far the highest among countries in the ‘consanguinity belt’ which includes several countries of the Middle
East where the rate averages at 40 per cent. And these close cousin marriages are the leading cause of genetic disorders in Pakistan.
Currently there are about 350 different genetic disorders exists in all over the Pakistan. And hardly 10% of them are treatable and rest of
them are either not treatable or very costly to cure them.
References
1. https://www.genome.gov/19016930/faq-about-genetic-disorders/
2. https://www.genome.gov/10001204/specific-genetic-disorders/
3. Genetic deafness in Pakistani population, Ghazanfar Ali
4. https://learn.genetics.utah.edu/content/disorders/singlegene/
