Genetics

What is Genetics?

Genetics is the study of heredity. Heredity is a biological process where a parent passes certain genes onto their children or offspring. Every child inherits genes from both of their biological parents and these genes in turn express specific traits. Some of these traits may be physical for example hair and eye color and skin color etc. On the other hand some genes may also carry the risk of certain diseases and disorders that may pass on from parents to their offspring.

Genes in the cell

The genetic information lies within the cell nucleus of each living cell in the body. The information can be considered to be retained in a book for example. Part of this book with the genetic information comes from the father while the other part comes from the mother.

Chromosomes

The genes lie within the chromosomes. Humans have 23 pairs of these small thread-like structures in the nucleus of their cells. 23 or half of the total 46 comes from the mother while the other 23 comes from the father.

The chromosomes contain genes just like pages of a book. Some chromosomes may carry thousands of important genes while some may carry only a few. The chromosomes, and therefore the genes, are made up of the chemical substance called DNA (DeoxyriboNucleic Acid). The chromosomes are very long thin strands of DNA, coiled up tightly.

At one point along their length, each chromosome has a constriction, called the centromere. The centromere divides the chromosomes into two ‘arms’: a long arm and a short arm. Chromosomes are numbered from 1 to 22 and these are common for both sexes and called autosomes. There are also two chromosomes that have been given the letters X and Y and termed sex chromosomes. The X chromosome is much larger than the Y chromosome.

Chemical bases

The genes are further made up of unique codes of chemical bases comprising of A, T, C and G (Adenine, Thymine, Cytosine and Guanine). These chemical bases make up combinations with permutations and combinations. These are akin to the words on a page.

These chemical bases are part of the DNA. The words when stringed together act as the blueprints that tells the cells of the body when and how to grow, mature and perform various functions. With age the genes may be affected and may develop faults and damages due to environmental and endogenous toxins.

Males and females

Women have 46 chromosomes (44 autosomes plus two copies of the X chromosome) in their body cells. They have half of this or 22 autosomes plus an X chromosome in their egg cells.

Men have 46 chromosomes (44 autosomes plus an X and a Y chromosome) in their body cells and have half of these 22 autosomes plus an X or Y chromosome in their sperm cells.

When the egg joins with the sperm, the resultant baby has 46 chromosomes (with either an XX in a female baby or XY in a male baby).

Genes and genetics

Each gene is a piece of genetic information. All the DNA in the cell makes up for the human genome. There are about 20,000 genes located on one of the 23 chromosome pairs found in the nucleus.

To date, about 12,800 genes have been mapped to specific locations (loci) on each of the chromosomes. This database was begun as part of the Human Genome Project. The project was officially completed in April 2003 but the exact number of genes in the human genome is still unknown.

History of Genetics

Genomics involves the study of genes, genetics, inheritance, molecular biology, biochemistry, biological statistics and incorporates the knowledge of advanced technology, computer science and mathematics.

Mid to Late 19th Century

The origins of genetics lie in the development of theories of evolution. It was in 1858 that the origin of species and how species variability was developed after the research work of Charles Darwin and Wallace. They described how new species arose via evolution and how natural selection occurred to evolve new forms. They however did not know the role genes had to play in this phenomenon.

Around the same time Gregor Mendel, an Austrian monk, was performing extensive experiments on inheritance and genetics of sweet pea plants. He described the unit of heredity as a particle that does not change and is passed on to offspring. His work is in fact the basis of understanding the principles of genetics even today. Consequently, Gregor Mendel is known as the Father of Genetics. There was, however, little awareness of Gregor’s work during this time.

Also in this period Haeckel correctly predicted that the heredity material was located in the nucleus. Miescher showed the material in the nucleus was a nucleic acid. Chromosomes as units carrying genetic information was also discovered around this time.

Early 20th Century

It was during this time that the Mendelian Principles and the Chromosomal Theory of Inheritance was established. Mendel’s work was largely unknown. It was not until 1900 that there was a rediscovery of the Mendelian principles and publications began citing his work.

Development of the chromosomal theory led to advent of the field of cytogenetics. The first observations of chromosomal abnormalities (e.g. duplications, deletions, translocations, inversions) were reported around this time.

Mid 20th Century

It was in 1870s that the material in the nucleus was determined to be a nucleic acid. DNA was determined to be the genetic material between 1920s and mid-1950s. Griffith’s experiments with a bacterial strain established the theory.

Avery, MacLeod and McCarty further showed that DNA, not protein or RNA was the factor responsible for genetic inheritance and evolution of the bacterial strains studied by Griffith.

It was then that Watson and Crick in their groundbreaking work determined the structure of DNA, and others suggested that DNA contained a genetic code.  The code was discovered in the 1960’s. Crick discovered the process of transcription and translation and led to formation of the “central dogma of molecular biology”.

Mid-late 20th Century and the Early 21st Century

This period heralded the concept of molecular biology and molecular genetics. Various advanced technologies made their way into knowledge base around this time. This included molecular biology, recombinant DNA technology, and biotechnology methods.

Methods of radiolabelling of the DNA with radioactive or fluorescent tags for development of diagnostic and therapeutic methods as well as research tools were discovered during this time.

Restriction enzymes were discovered and used to construct recombinant DNA molecules that contained foreign DNA that could be grown in abundance in bacterial strains.

Then came methods like PCR (Polymerase chain reaction) and host of other biotechnology methods and new applications were found in medicine, pharmacotherapeutics as well as research.

Mid to Late 19th Century: Evolution, Natural Selection, Particulate Inheritance and Nuclein 1858

  • Darwin and Wallace - Role of natural variation and natural selection in evolution
  • 1865 -  Gregor Mendel - Particulate inheritance
  • 1866 - Ernst Haeckel;  Heredity materials was in the nucleus
  • 1871 -  Friedrich Miescher;  Material in the nucleus was a nucleic acid

Early 20th Century: Mendelian Principles are extended and the Chromosomal Theory of Inheritance solidifies

  • 1900 - Correns, de Vries, von Tschermak - Mendel’s work is rediscovered;The age of genetics begins
  • 1902 - Walter Sutton and Theodor Boveri - Chromosomal Theory of Inheritance; The heredity material resides in chromosomes
  • 1905-1923
    • Linkage
    • Sex linkage
    • Genetic mapping
    • Number of linkage groups - number of chromosomes
    • Lethal genes
    • Maternal inheritance
  • 1908 - Hardy and Weinberg - Hardy-Weinberg principle of genetic equilibrium
  • 1909 - Nilsson-Ehle - Theory of quantitative traits and quantitative genetics

Mid 20th Century: DNA is the stuff of life; the preeminence of the Darwinian theory of evolution via natural selection is confirmed

  • 1928 - Griffith - Transformation experiments
  • 1944 - Avery, MacLeod, McCarty - Definitive proof that DNA is the genetic material
  • 1953 - Watson and Crick - DNA structure is defined
  • 1954-1961
    • DNA code is determined
    • Transcription is described
    • Replication is described
    • Translation is described
    • Operons are discovered
  • 1932-1953
    • Fisher and Dobzhansky - The Modern Synthesis is formulated
    • Links Darwinian evolutionary theory and Mendelian genetics
  • 1968
    • Kimura
    • Neutral Theory of Molecular Evolution is introduced

Mid-late 20th  Century and the Early 21st Century: The Age of Molecular Genetics; Phylogenetics Studies Intensive; The Information Age; The Emergence of Genomics Science

  • 1969 - ARPANET - Internet comes on line
  • 1970 - Arber and Smith - First restriction enzyme, Hind II, is isolated
  • 1970 - Baltimore and Temin - Discovery of reverse transcriptase
  • 1972 - Berg - First recombinant DNA molecule is constructed
  • 1973 - Boyer and Cohen - First functional recombinant E. coli cell produced
  • 1977 - Sanger and Gilbert - DNA sequencing techniques are described
  • 1977 - Sharp and Roberts - Introns discovered
  • 1978 - Botstein - RFLPs launch the era of molecular mapping of linkage groups
  • 1980 - Sanger Group - First genome is sequenced, the bacteriophage ΦX174 of E. coli
  • 1983 - Mullis - PCR technique is discovered
  • 1986 - Hood, Smith, Hunkapiller and Hunkapiller - First automated DNA sequencer
  • 1990 - US Government - Human Genome Project launched
  • 1995 - Celera - First bacterial genome (H. influenza) is sequenced
  • 1996
    • Yeast Genome Consortium
    • First eukaryotic genome (yeast) sequenced 
  • 2000 - Arabidopsis Genome Initiative - First flowering plant genome (Arabidopsis thaliana) is  sequenced
  • 2001 - The human genome sequence is published

 

Genetics and Gene Expression

The human genome is made up of about 20,000 genes located on one of the 23 chromosome pairs found in the nucleus or on long strands of DNA located in the mitochondria. 

The Human Genome Project and genetic research

To date, about 12,800 genes have been mapped to specific locations (loci) on each of the chromosomes. This database was begun as part of the Human Genome Project. The project was officially completed in April 2003 but the exact number of genes in the human genome is still unknown.

It will still take many years to find all the genes as well as understand the need and use of the non-coding DNA. Genetic research also focuses on the effects of the environment on genes and their expression.

The genetic code

Each gene has its own specific location on the chromosome or on the mitochondrial DNA. The gene performs a single important function. These serve as blueprints for a physical, physiological or mental trait. The genes tell how a person looks like hair, eye, skin color, shape of the body and features, height etc.

The DNA code is made up of very long chains of four basic building blocks (nucleotide bases): 

  • Adenine (A)
  • Guanine (G)
  • Thymine (T)
  • Cytosine (C)

The chromosome contains two of the DNA chains running in opposite directions; the bases pair up to form the rungs of a ladder twisted into a double helical structure.

Adenine (A) can only pair with base Thymine (T), and vice versa; and base Guanine (G) can only pair with base Cytosine (C), and vice versa. There are nearly three billion of these base pairs of DNA to make the human genome. Within the DNA, three of these four chemical ‘letters’ A, G, C and T (a triplet) form a codon. A particular codon codes for an amino acid and sequences of amino acids code for a protein.

DNA that makes up the genes is often called ‘coding DNA’. Between two genes is a region of DNA that does not code for any protein. This is called the ‘non-coding DNA’ and was initially termed ‘junk DNA’ as it appeared that this DNA did not contain the information required for proteins.

Now new research shows that this region may not be junk and may be important for certain functions. That role is still largely unknown but they may play a regulatory role in gene expression. Studies of this non-coding DNA are useful for forensic investigations like paternity suits and criminal investigations etc.

Genetic expression

The genetic code codes for proteins. The information of the DNA is ‘translated’ into a chain of amino acids that forms a protein. These proteins form the building blocks for structures within the cells and ultimately the whole body. Proteins also form enzymes and other chemicals that perform various functions in the body. Each gene can code for different proteins and thus the number of proteins known to exist in the cells is more than the number of genes.

All genes are not expressed or do not code for any protein. This could be organ specific for example a liver cell expresses different genes than kidney cells.

The environment also plays a role in determining the ultimate trait. The phenotype of an organism thus depends on the interaction of genetics with the environment. The environment for example, has a role in effects of the human genetic disease phenylketonuria. The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acid phenylalanine. This leads to toxic build-up of an intermediate molecule leading to mental retardation and seizures. Persons with phenylketonuria mutation on a strict diet that avoids this amino acid may remain normal and healthy.