INTRODUCTION TO

MEDICAL GENETICS
DR OKEKE EMMANUEL
OUTLINE
• INTRODUCTION
• HSITORY OF GENETICS
• DEFINITION OF TERMS
• IMPORTANCE OF GENETICS
• CONCLUSION
Introduction
• Humans have known for many years, that traits can be transferred
from parents to an offspring.

• The concepts of an offspring taking after their parents has since then
been studied.

• As genetic information passes to the offspring several processes and

molecules are involved and little alteration of any of these molecules
can lead to disease
Introduction 2
• Genetics is the branch of biology that deals with the study of
heredity/ inheritance and its biological process. It involves the study
of genes, genomes and the cell cycle.

• William Bateson coined the word “Genetic” in 1906 and defined it

thus

“ Genetics is the science dealing with heredity and variation, seeking to

discover laws governing similarities and differences in individuals
related to descent.”
History of Genetics
• The history of genetics can be broadly viewed as Pre-Mendelian,
Mendelian and Post-Mendelian.

• Genetics is not new, people have been practicing genetics research since
long before they knew what DNA, genes or genetics were for thousands
of years.

• These can be seen from selective breeding of animals and plants that
gave the highest breed, are more disease resistant and grow within a
short time over others that do not have the above characteristics.
History of Genetics - 2
History of Genetics - 3
Pre - Mendelian
• Hippocrates in 400BC stated that representative element of the parent’s
body, even those acquired, are present in the semen. These elements
provide the building block for the corresponding parts of the embryo.

• Aristotle (384 – 322 BC) refuted the theory put forward by Hippocrates
by pointing out that some crippled, mutilated parents do not always
have abnormal offspring. He believed the father’s semen provides the
plan (form) according to which the amorphous blood of the mother is
shaped into the offspring(substance).
Pre- Mendelian 2
• Aristotle recognized that inheritance involved the transmission of
information and not simply a transmission of body part.

• 17th and 18th centuries, new theories of inheritance were propounded.

• Preformation theory - either the egg or sperm contains the entire

organism in a miniaturized form.
• Theory of Epigenesis - put forward by Christian Wolff (1679 – 1754) –
arose from the observation that adult structures developed form
embryonic tissues which do not resemble corresponding adult structures.
Mendelian
• Between 1856 and 1865, Gregor Johan Mendel – An Austrian Monk,
carried out a study on garden pea, Pisum sativum and traced the
inheritance patterns of certain characteristics.
• Through his work, Mendel saw that the genotype and phenotype of the
progeny were predictable and some traits are dominant over others.
• His work was published in 1866 and clearly stated the laws of inheritance
which can be derived from his results.
• Inspite of the fundamental nature of his work, it had no immediate
impact on the scientific world. Hugo de Vries and Carl Correns later re-
discovered Mendel’s work.
Mendelian 2
Post – Mendelian
• Provisional hypothesis of pangenesis – Charles Darwin

• GermPlasm Theory 1885

• Oscar, Hertwig (1849) and later Herman Fol, and Edward Strasbuger
described the process of fertilization including the fusion of the egg
and the sperm nuclei

• Chromosomes was described by Waldeyer 1888

Post- mendelian 2
• Fleming, Strasbuger and Van Beneen described chromosomes and their
division in mitosis as well as their constancy in number
• Thomas Hunt Morgan shoed that genes are located on chromosomes
1910
• Hertwig and Strasbuger later developed a theory that the nucleus
contains hereditary materials.
• Weisman postulated that during gamete formation, the chromosomes
number is halved, the process involved in meiosis. If that were not so,
there would be a doubling of the chromosome at each fertilization. This
was also observed by Boveri and other investigation.
Post – Mendelian 3
• James Watson and Francis crick described the structure of DNA 1953
• Levan and Tijo reported the human chromosome number was 46
• Sanger sequencing was developed 1977
• Polymerase chain reaction by Kerry Mullis 1985
• Human genome project was launched 1990
 DEFINITION OF TERMS
• Chromosome – are threadlike structures made of protein and a single
molecule of DNA that serve to carry the genomic information from cell to cell.
Chromosomes resides in the nucleus of cells.

• DNA – Deoxyribonucleic acid is the molecule that carries genetic information

for the development and functioning of an organism. It is made up of two
linked strands wound around each other to resemble a twisted ladder - the
double helix. Each backbone is made of alternating sugar and phosphate
groups . Attached to each base is one of four bases. The two strands are
connected by chemical bonds between the bases. The sequence of the bases
along DNA’s backbone encodes biological information such as instructions to
DEFINITION OF TERMS 2
• Histones - A histone is a protein that provides structural support for a
chromosome. Each chromosome contains a long molecule of DNA, which must fit
into the cell nucleus. To do that, the DNA wraps around complexes of histone
proteins, giving the chromosome a more compact shape. Histones also play a role
in the regulation of gene expression.

• Gene - The gene is considered the basic unit of inheritance. Genes are passed
from parents to offspring and contain the information needed to specify physical
and biological traits. Most genes code for specific proteins, or segments of
proteins, which have differing functions within the body. Humans have
approximately 20,000 protein-coding genes.
• Locus -A locus, as related to genomics, is a physical site or location within a
genome (such as a gene or another DNA segment of interest), somewhat like a
DEFINITION OF TERMS 3
DEFINITION OF TERMS 4
• Codons - A codon is a DNA or RNA sequence of three nucleotides (a trinucleotide)
that forms a unit of genomic information encoding a particular amino acid or
signaling the termination of protein synthesis (stop signals). There are 64 different
codons: 61 specify amino acids and 3 are used as stop signals.

• An intron is a region that resides within a gene but does not remain in the final
mature mRNA molecule following transcription of that gene and does not code
for amino acids that make up the protein encoded by that gene. Most protein-
coding genes in the human genome consist of exons and introns.
• An exon is a region of the genome that ends up within an mRNA molecule. Some
exons are coding, in that they contain information for making a protein, whereas
others are non-coding. Genes in the genome consist of exons and introns.
DEFINITION OF TERMS 5
DEFINITION OF TERMS 6
DEFINITION OF TERMS 7
• Alleles- one of two or more versions of DNA sequence at a given
genomic location. An individual inherits two alleles, one from each
parent, for any given genomic location where such variation exists.
Homozygous allele – when the alleles are the same, heterozygous –
when different.

• Dominant allele - In the case of a dominant trait, only one copy of the
dominant allele is required to express the trait. The effect of the other
allele (the recessive allele) is masked by the dominant allele. Typically,
an individual who carries two copies of a dominant allele exhibits the
same trait as those who carry only one copy
DEFINITION OF TERMS 8
• In the case of a recessive trait, the alleles of the trait-causing gene are the same, and both
(recessive) alleles must be present to express the trait. A recessive allele does not produce a
trait at all when only one copy is present.

• Transcription - Transcription, as related to genomics, is the process of making an RNA copy of a

gene’s DNA sequence. This copy, called messenger RNA (mRNA), carries the gene’s protein
information encoded in DNA. In humans and other complex organisms, mRNA moves from the
cell nucleus to the cell cytoplasm (watery interior), where it is used for synthesizing the
encoded protein.

• Translation - Translation, as related to genomics, is the process through which information

encoded in messenger RNA (mRNA) directs the addition of amino acids during protein
synthesis. Translation takes place on ribosomes in the cell cytoplasm, where mRNA is read and
translated into the string of amino acid chains that make up the synthesized protein
DEFINITION OF TERMS 9
 DEFINITION OF TERMS 10
• Genome -The genome is the entire set of DNA instructions found in a cell. In humans, the
genome consists of 23 pairs of chromosomes located in the cell’s nucleus, as well as a small
chromosome in the cell’s mitochondria. A genome contains all the information needed for an
individual to develop and function

• Genotype - A genotype is a scoring of the type of variant present at a given location (i.e., a
locus) in the genome. It can be represented by symbols. For example, BB, Bb, bb could be used
to represent a given variant in a gene. Genotypes can also be represented by the actual DNA
sequence at a specific location, such as CC, CT, TT. DNA sequencing and other methods can be
used to determine the genotypes at millions of locations in a genome in a single experiment.
Some genotypes contribute to an individual’s observable traits, called the phenotype.

• Traits – physical attributes or characteristics. A trait, as related to genetics, is a specific

characteristic of an individual. Traits can be determined by genes, environmental factors or by a
combination of both. Traits can be qualitative (such as eye color) or quantitative (such as height
or blood pressure). A given trait is part of an individual’s overall phenotype.
DEFINITION OF TERMS 12
• Mutation - A mutation is a change in the DNA sequence of an
organism. Mutations can result from errors in DNA replication during
cell division, exposure to mutagens or a viral infection. Germline
mutations (that occur in eggs and sperm) can be passed on to
offspring, while somatic mutations (that occur in body cells) are not
passed on.
• Also called misspelling
• Can be silent (no symptoms) or profound
• An example is a single gene mutation in single nucleotide.
DEFINITION OF TERMS 13
• A point mutation is a gene mutation that changes a single nucleotide or just a few
nucleotides in the DNA sequence. In other words, at least one nucleotide gets
messed up. They show up at a single point in a DNA sequence.

• These mutations can be base substitutions, deletions, or insertions.

• Substitution mutations cause a single base pair to be exchanged for another. They
can cause:
• Silent mutations: The substitution doesn't change the amino acid that the codon
codes for.
• Missense Mutations: The substitution changes the codon so that it corresponds to a
different amino acid than it should.
• Nonsense Mutations: The substitution changes the codon so that it signals an early
stop of translation.
DEFINITION OF TERMS 14
• Insertion mutations happen when an extra base is inserted into a
sequence.

• Deletion mutations happens when a base is removed from the

sequence. These changes can cause:

• Frameshifts mutations: When a base is added or removed, the entire

codon sequence following the mutation changes
DEFINITION OF TERMS 15
DEFINITION OF TERMS 16
DEFINITION OF TERMS 16

• Autosomal dominant – is a pattern of inheritance of genetic disorder

in which a copy of mutated gene is enough to cause the disorder. E.g
BRCA 1 gene in breast cancer.

• Autosomal recessive - is a pattern of inheritance of some genetic

disorders which requires two copies of the mutated gene to cause the
disorder.
• X-LINKED mutations: Mutations on the genes on the X chromosomes
Role of Medical Genetics
• Diagnosis of genetic diseases.
• Gene therapy
• Precision medicine – personalization of medical treatment
• Risk predictor of developing genetic and non-genetic diseases.
• Vaccine development
• Genetic counselling
• Pharmcogenetics
CONCLUSION
• Medical genetics has come a long way since humans began
understanding how inherited traits affected health and survival of
plants and animal.

• Medical genetics is crucial for understanding and addressing genetic

disorders.

• Ongoing research and technological advancements hold promise for

improved diagnosis and treatment.
THANK YOU