◉ Lecture #1

◉ Department of Special Clinical Disciplines

Introduction to medical genetics

GENETICS is the science that deals with heredity and
variation in organisms, including the genetic features and
constitution of a single organism, species, or group, and
with the mechanisms by which they are effected
Genes are contained in chromosomes in the cell nucleus and mitochondria.

In humans, somatic (nongerm) cell nuclei normally have 46 chromosomes in

23 pairs.

Each pair consists of one chromosome from the mother and one from the
father.

Twenty-two of the pairs, chromosome numbers 1 to 22, the autosomes, are

normally homologous (identical in size, shape, and position and number of
genes).

The 23rd pair, the sex chromosomes (X and Y), determines a person’s
sex as well as containing other functional genes.

Women have 2 X chromosomes (which are homologous) in somatic cell

nuclei; men have one X and one Y chromosome (which are heterologous).
⦿ Gene – basic unit of genetic information.
Genes determine the inherited
characters.
⦿ Genome – the collection of genetic
information.
⦿ Chromosomes – storage units of genes.
⦿ DNA - is a nucleic acid that contains
the genetic instructions specifying the
biological development of all cellular
forms of life
Most human cells
contain 46 chromosomes:

⦿2 sex chromosomes (X,Y):

XY – in males.
XX – in females.

⦿ 22 pairs of chromosomes named autosomes.

 sister
chromatids
telomeres
centromere

unreplicated replicated
chromosome chromosome
Each chromatid consists of a very long strand of DNA. The DNA i
roughly collinear with the chromosome but is highly structured arou
histones and other proteins which serve to condense its length and
control the activity of genes.
Centromere

A region within chromosomes

that is required for proper
segregation during meiosis
and mitosis.

Telomeres
Specialized structures at
chromosome ends that are
important for chromosome
stability.
The X chromosome carries genes responsible for many hereditary traits

The Y chromosome carries genes that initiate male sex differentiation. Because
the X chromosome has many more genes than the Y chromosome, many X
chromosome genes in males are not paired; in order to maintain a balance of
genetic material between men and women, one of the X chromosomes in each
cell of females is randomly inactivated early in fetal life.

In some cells, the X from the mother is inactivated, and in others it is the X from
the father.

Once inactivation has taken place in a cell, all descendants of that cell have the
same X inactivation.

A karyotype illustrates the full set of chromosomes in a person’s cells.

Germ cells (egg and sperm) divide through meiosis, which
reduces the number of chromosomes to 23—half the
number in somatic cells. In meiosis, the genetic
information inherited from a person’s mother and father
is recombined through crossing over (exchange between
homologous chromosomes).

When an egg is fertilized by a sperm, the normal number

of 46 chromosomes is reconstituted.
Genes are arranged linearly along the DNA of chromosomes.
Each gene has a specific location (locus), which is typically the
same on each of the 2 homologous chromosomes.

The genes that occupy the same locus on each chromosome

of a pair (one inherited from the mother and one from the
father) are called alleles.

Each gene consists of a specific DNA sequence.

Having a pair of identical alleles for a particular gene is

homozygosity having a pair of nonidentical alleles is
heterozygosity.
 Structure of DNA

• Slide bullet text

Genes consist of DNA. The length of the gene determines the length of the
protein synthesized from the gene code. DNA is a double helix in which
nucleotides (bases) are paired:

Adenine (A) is paired with thymine (T)

Guanine (G) is paired with cytosine (C)

DNA is transcribed during protein synthesis, in which one strand of DNA is

used as a template against which messenger RNA (mRNA) is synthesized.

RNA has the same base pairs as DNA, except that uracil (U) replaces
thymine (T).
Parts of mRNA travel from the nucleus to the cytoplasm and
then to a ribosome, where protein synthesis occurs. Transfer
RNA (tRNA) brings each amino acid back to the ribosome where
it is added to the growing polypeptide chain in a sequence
determined by the mRNA.

As a chain of amino acids is assembled, it folds upon itself to

create a complex 3-dimensional structure under the influence of
nearby chaperone molecules.
The code in DNA is written in triplets containing 3 of the 4
possible nucleotides.

Specific amino acids are coded by specific triplets termed

codons.

Because there are only 20 amino acids, there are redundant (extra)
triplet combinations.

Some triplets code for the same amino acids as other triplets.

Other triplets may code for elements such as instructions to start

or stop protein synthesis and the order in which to combine and
assemble amino acids.
Genotype refers to a specific genetic composition and sequence; it determines
which proteins are coded for production.

Genome refers to the entire composition of a set of haploid chromosomes

(single strand), including the genes they contain.

Phenotype refers to the entire physical, biochemical, and physiologic makeup

of a person—how the cell (the body) functions. Phenotype is determined by the
types and amounts of proteins actually synthesized, how the genes are actually
expressed. Specific genotypes may or may not correlate well with phenotype.

Expression refers to the process in which the information encoded in a gene is

used to control the assembly of a molecule (usually protein or RNA). Gene
expression depends on multiple factors such as whether a trait is dominant or
recessive, the penetrance and expressivity of the gene
1.Single gene disorders are caused by DNA changes in one particular gene, and often have
predictable inheritance patterns.

2.Multifactorial traits -The type of hereditary pattern seen when there is more than one genetic factor
involved and there are also environmental factors participating in the causation of a condition

3.Chromosomal abnormalities (diseases where the phenotypes are largely determined by physical
changes in chromosomal structure - deletion, inversion, translocation, insertion, in chromosome
number - trisomy or monosomy, or in chromosome origin - uniparental disomy)

4.Mitochondrial inheritance (diseases where the phenotypes are affected by mutations of

mitochondrial DNA)

5. Congenital malformations (congenital defects of inner organs or parts of body)

1. Deletion during cell division,
especially meiosis, a piece of
the chromosome breaks off,
may be an end piece or a
middle piece (when two breaks
in a chromosome occur).
2. Inversion a segment of the
chromosome is turned 180°,
same gene but opposite
position
3.Translocation movement of a
chromosome segment from one
chromosome to a non-homologou
chromosome
4.Duplication - a doubling of
a chromosome segment
because of attaching a broken
piece form a homologous
chromosome, or by unequal
crossing over.
ifferent categories: dominant, recessive and X-linked.

s that occur in the heterozygous state – when an individual has one muta

family trees, from parent to child.

on’s disease
• Recessive diseases are single gene disorders that only
occur in the homozygous state - when an individual carries
two mutant versions (alleles) of the relevant gene.

• The effects of the healthy allele can compensate for the

effects of the mutant allele. The mutant allele does not
cause disease symptoms when a healthy allele is also
present. However, if a parent inherits two mutant alleles,
there are no healthy alleles, so the mutant allele can exert
its effect.

• Example is Sickle cell disease

• X-linked disorders are single gene disorders that result
from the presence of a mutated gene on the X
chromosome

• Because females (XX) have two copies of the

X chromosome but males (XY) only have one copy, X-
linked disorders are more common in males. If a male’s
single copy on the X chromosome is mutated he has no
healthy copy to restore healthy function.

• X-linked disorders can be either recessive or dominant.

⦿ Affected males pass the disorder to all
daughters but to none of their sons.
⦿ Affected heterozygous females
married to unaffected males pass the
condition to half their sons and
daughters
⦿ Many more males than
females show the
disorder.
⦿ All the daughters of an
affected male are
“carriers”.
⦿ None of the sons of an
affected male show
the disorder or are
carriers.
⦿ e.g., hemophilia

⦿ If the locus is on the X

chromosome and both
alleles must be mutant
alleles to express the
phenotype in females
This type of inheritance applies to
genes in mitochondrial DNA
Mitochondrial disorders can
appear in every generation of a
family and can affect both males
and females, but fathers do not
pass mitochondrial traits to their
children.
E.g. Leber's hereditary optic
neuropathy (LHON)
Standard pedigree symbols
Male, Male, heterozygous for
affected autosomal recessive trait

Female, Female, heterozygous for

unaffected Autosomal or X-linked
recessive trait
Male,
deceased Dizygotic
(non-identical)
twins
Mating
Monozygotic
(identical)
Consanguineous twins
mating
Spontaneous abortion
Pregnancy or still birth
Or multifactorial

The most common yet still the least understood of human

genetic diseases

Result from an interaction of multiple genes, each with a

minor effect

The susceptibility alleles are common

Type I and type II diabetes, autism, osteoarthritis

Thank you for attention!