Human Genetics- Complete guide to single gene , autosomal anomalies and Polygenic traits (HEC Syllabus )

By Momina Shehzadi | BS Zoology Graduate, Pakistan

In this article, we will learn Introduction to Human Genetics in simple words - Single Gene Disorders, Autosomal Anomalies, and Polygenic Traits. This topic is very important for BS Zoology, BSc, MSc and FSc students according to HEC Syllabus Pakistan.

Human Genetics is the most important and scoring chapter for BS Zoology, BSc, MSc and FSc students according to HEC Syllabus Pakistan. The study of transmission of human traits from parents to children is called Human Genetics.

In simple words, the branch of genetics which deals with the inheritance of characters in man is termed as human genetics. It deals with physical, mental, normal and abnormal characters pertaining to an individual or a population. The characters are established and express themselves during development and are influenced by many environmental factors.

Sir Archibald Garrod, a British physician was the pioneer of human genetics. In 1901, he pointed out that certain inborn errors of metabolism like phenylketonuria, alkaptonuria, etc., are controlled by genes and are inherited in simple Mendelian fashion. The basic principles of inheritance as applicable to all other organisms are equally applicable to man.

Why Man is not a Favorable material for Genetic Studies?

Though human genetics was established in 1901, no significant work was done in early years because man is not a favorable object for genetic studies due to following reasons:

1. No controlled Breeding:

 Controlled breeding experiments under standardized environment are impossible because of social and ethical hindrance.

2. Small Family Size:

Number of offspring of each marriage is very small so that statistical computations are not possible.

3.Long life Span:

Life span of man is long. As a result, results cannot be studied for three or more generations quickly.

4. Heterozygosity:

Majority of human beings are genetically heterozygous for many characters. Therefore, it is difficult to get isogenic strains.

5. Late Maturity:

 Humans attain sexual maturity very late.

In recent years, development of newer techniques like karyotyping, pedigree analysis, DNA sequencing, amniocentesis and genetic counseling has helped in understanding mechanism of inheritance of many characters in man.

What are Genetic Disorders?

A genetic disease is any disease caused by an abnormality in the genetic makeup of an individual. The genetic abnormality can range from minimum to major, from a discrete mutation in a single base in the DNA of a single gene to a gross chromosomal abnormality involving addition or subtraction of an entire chromosome or set of chromosomes.

Some people inherit genetic disorders from parents, while acquired changes or mutations in a preexisting gene cause other genetic diseases. Genetic mutations can occur either randomly or due to environmental exposure like radiation and chemicals.

Types of Genetic Disorders:

There are 4 different types of genetic disorders:

1. Single gene inheritance (Monogenic or Mendelian inheritance)

2.Multifactorial inheritance  (Polygenic + Environmental)

3.Chromosomal abnormalities (Autosomal anomalies)

4. Mitochondrial inheritance 

1) SINGLE GENE DISORDERS (MONOGENIC DISEASE)

The disorders which are controlled by single factor or gene are called single factor disorders. Most human genetic diseases are polygenic, but even a single base-pair change in one of 20,000 human genes can lead to serious inherited disorder.

A single-gene disorder is result of a single mutated gene. Most congenital metabolic disorders as inborn errors of metabolism result from single-gene defects.

Patterns of single gene inheritance:

a) Autosomal Dominant Inheritance:

 In it only one copy of a defective gene (from either parent) is necessary to cause the condition. If one parent has it, 50% children will have it. Example: Brachydactyly (short fingers and toes), Marfan syndrome, Huntington's disease.

b) Autosomal Recessive Inheritance:

 In it two copies of defective gene (one from each parent) are necessary to cause the condition. Parents are usually carriers and normal. Example: Sickle cell anemia, Cystic fibrosis, Thalassemia, Phenylketonuria, Alkaptonuria.

C) X- linked Inheritance:

Defective gene is present on X-chromosome. It may be dominant or recessive. Criss-cross inheritance is seen. Example: Haemophilia, Color blindness, Fragile X syndrome.

Pseudoautosomal  Genes: These are genes present on both X and Y chromosomes at their tips. They behave like autosomal genes and can recombine between X and Y during meiosis. They do not show sex-linked inheritance.

Detailed Examples of Single Gene Disorders (HEC Syllabus Topics)

I) Sickle Cell Anemia:

It is an autosomal recessive single gene disorder common in Africa and Pakistan. It is caused by mutation in 6th codon of beta-globin gene on chromosome 11. Glutamic acid is replaced by valine. As a result, RBCs become sickle-shaped instead of biconcave. Sickle cells cannot carry enough oxygen and block blood vessels, causing severe pain, anemia, and organ damage. Heterozygous individuals are resistant to malaria.

ii) Brachydactyly

It is an autosomal dominant trait in which fingers and toes are abnormally short. Person has one defective copy. It was one of first traits in humans proved to be Mendelian.

iii) Phenylketonuria (PKU):

It is classic example of inborn error of metabolism. It is autosomal recessive. Normally, enzyme phenylalanine hydroxylase converts amino acid phenylalanine to tyrosine. In PKU patients, this enzyme is absent due to gene mutation on chromosome 12. So phenylalanine accumulates in blood and converts to phenylpyruvic acid which is excreted in urine. Excess phenylalanine in brain causes severe mental retardation, light skin and hair. Early diagnosis and diet low in phenylalanine can prevent retardation.

iV) Alkaptonuria:

Another inborn error of metabolism. It is also autosomal recessive. Enzyme homogentisic acid oxidase is absent. So homogentisic acid cannot be converted to maleylacetoacetic acid. Homogentisic acid accumulates and urine turns black on exposure to air. Later, joints turn black and arthritis occurs. Garrod studied this disease.

2) Autosomal Anomalies (Chromosomal abnormalities)

These are caused by changes in number or structure of autosomes. Human has 22 pairs of autosomes. Anomalies can be due to nondisjunction during meiosis.

Types of chromosomal Mutations:

a) Aneuploidy: Addition or loss of one chromosome. Example: Trisomy (2n+1) like Down syndrome, Monosomy (2n-1) like Turner syndrome.

b) Euploidy: Loss or addition of whole set. Example: Triploidy.

Importance of Autosomal Anomalies:

Down Syndrome (Trisomy 21): Most common autosomal trisomy. Incidence 1 in 700 births. Person has 47 chromosomes with 3 copies of chromosome 21. Karyotype 47, XX, +21 in female and 47, XY, +21 in male. Cause is nondisjunction in mother, risk increases with maternal age. After 40 years, risk is 1 in 100. Symptoms include small head, flat face, small ears, short neck, mental retardation, heart defects. No cure, but early physiotherapy helps. Gene dosage effect: chromosome 21 has 230 genes, extra copy causes over-expression of APP, SOD1, DYRK1A genes leading to Alzheimer's and learning problems.

Edwards Syndrome (Trisomy 18)

Second most common trisomy. Babies have small head, small jaw, heart defects, severe intellectual disability. Most die within first year.

Patau  Syndrome ( Trisomy 13)

Severe defects of brain, heart and cleft lip/palate.

Gene Mutation and Disorders:

 Mutation is sudden change in structure of gene. Types include point mutation (silent, missense, nonsense, frameshift), somatic vs germinal, dominant vs recessive, beneficial, lethal, biochemical mutations. Biochemical mutations affect metabolic pathways as one gene one enzyme concept.

3. Complex Inheritance -polygenic Traits  (Most Important for HEC)

Polygenic inheritance, also known as quantitative inheritance, refers to a single inherited phenotypic trait that is controlled by two or more different genes. Many human traits are polygenic and also influenced by environment, so they are called multifactorial.

Genes follow Mendel's laws individually but don't produce typical 3:1 ratios because they contribute equally and are neither dominant nor recessive with respect to each other.

Characteristics of polygenic inheritance:

I)Character can be quantified by measuring, weighing or counting.

ii) Effects of each contributing gene are cumulative or additive.

iii) Each contributing allele produces equal effect.

iV) No dominance, no epistasis, no linkage.

V) Analysis requires large number of progenies.

Vi) Shows continuous variation and bell-shaped curve.

Vii) Environmental effects influence expression.

1. Cleft Lip and Cleft Palate:

This is best example of multifactorial inheritance. Cleft lip is gap in upper lip, cleft palate is opening in roof of mouth. Both occur due to failure of fusion of facial processes during embryonic development. 

2. Human Height:

Height is controlled by over 400 genes. 

Skin color is influenced by pigment melanin. More melanin means darker skin. At least three genes control skin color, with other modifiers. Albino people produce no melanin.

4.Human Eye color:

Eye color is polygenic. Two major genes OCA2 and HERC2 on chromosome 15 plus 13 other genes control it. Iris has melanin.

Location of polygenes:

 James Crow studied DDT resistance in Drosophila and proved polygenes are dispersed over whole genome, each chromosome contains loci that contribute to phenotype.

Significance of Inheritance:

1. It proves Mendelian rules can explain continuous traits.

2. Important in agriculture for better, bigger, high-yielding varieties.

3. Many human traits like height, weight, IQ, skin color are polygenic.

4. Helps understand multifactorial diseases like diabetes, hypertension, heart disease.

Conclusion 

Human genetics is vast field. Single gene disorders like sickle cell anemia, PKU, alkaptonuria follow Mendelian inheritance. Autosomal anomalies like Down syndrome are due to trisomy. Polygenic traits like cleft lip, cleft palate, height, skin color and eye color show quantitative inheritance with environmental influence. Understanding these concepts is essential for genetic counseling to estimate recurrence risk and for better management of genetic diseases.

FAQs for Students:

Q1: What is difference between single gene and multifactorial disorders?

Ans: Single gene disorder caused by one gene mutation with Mendelian pattern. Multifactorial disorder caused by many genes plus environment, shows continuous variation and no fixed ratio.

Q2: What are pseudoautosomal genes?

Ans: Genes present on tips of both X and Y chromosomes that can recombine and behave like autosomal genes, not showing sex-linked inheritance.

Q3: Why cleft lip is called multifactorial?

Ans: Because it is caused by interaction of many genes plus environmental factors like drugs, smoking, folic acid deficiency during pregnancy.

Q4: What is gene dosage effect in Down syndrome?

Ans: In trisomy 21, every gene on chromosome 21 is present in three copies and expressed 1.5 times more than normal, causing combined over-expression of 230 genes leading to syndrome features.

Also read previous complete topic Human genetic Syndromes 

Written by Momina Shehzadi, BS Zoology Graduate from Pakistan.