Introduction to Genetics in the Twenty-First Century

Course Number: 0504321

CHAPTER
1
Medical Genetics
Sundays: 2:30-3:30
Tuesday 3:30-4:30

CHAPTER OUTLINE

▪ 1.1 DNA & gene: The Human Genome Project

▪ 1.2 The Relationship Between Genes and Traits
▪ 1.3 Genetic diversity
 A family portrait
with members of four generations

Why do some of the children

look like only one of the
parents, while some of the
other children look more
like the great, great
grandparents?
What causes the similarities
and differences of
appearance and the
skipping of generations?
Medical Genetics
Clinical Genetics-
subgroups concerned with
Clinical manifestation
Of genetic diseases

Molecular and biochemical Immunogenetics -

genetics - Cytogenetics -
the study of the
the study of the the study of the
genetics of the
structure and function structure of
immune
of individual genes. chromosomes.
system
.
Genetic epidemiology -
Population genetics -
the study of
the study of genetics
epidemiology of
of populations.
genetic disease.
 Introduction to Genetics
• GENETICS – branch of biology that deals with
heredity and variation of organisms.

• Chromosomes carry the hereditary

information (genes)
• Arrangement of nucleotides in DNA
• DNA → RNA → Proteins
• Chromosomes (and genes) occur in pairs
Homologous Chromosomes
• New combinations of genes occur in sexual
reproduction
– Fertilization from two parents
Allele for an eye color
Allele for another eye color
Meiosis
 Overview of Genetics
• Genetics – branch of biology that deals with heredity and
variation of organisms.
• The complete genetic composition of a cell or organism is
called a genome.
• The genome encodes all of the proteins a cell or
organism can make.
• Many key discoveries in genetics are related to the study
of genes and genomes.
• Medical genetics is the science of human biological
variation as it relates to health and disease
 What is a Gene???

• A gene, the basic unit of

inheritance; it is a
segment within a very
long strand of DNA with
specific instruction for the
production of one specific
protein.
• Genes located on a
chromosome on it's place
or locus.
 Mendelian Inheritance

• Alleles: are the individual copies of a particular gene.

• Genotype: genetic constitution of any individual with respect
to a particular trait.
• Phenotype: physical manifestation of a trait.
• Trait can be transmitted as autosomal or sex linked and as
Dominant or Recessive traits.
• Dominant allele: allele that mask or hides the expression of its
alternative .
• Recessive allele : the allele which is masked or hidden.
• Sex-Linked Genes: Genes located on a sex chromosome
 Three milestones in genetics

• Mendel – basic laws of inheritance – 1865

• Watson and Crick – structure of DNA – 1953

• Human Genome Project and Celera – sequence and

annotation of human genome - 2003
 Gregor Mendel discovered
the basic principles of genetics

• Mendel inferred laws of genetics that

allowed predictions about which
traits would appear, disappear, and
then reappear
• Mendel's paper "Experiments in
plant hybrids" was published in 1866
and became the cornerstone of
modern genetics
 Gregor Mendel discovered
the basic principles of genetics

• Mendel’s law of segregation: The two alleles for each

trait separate (segregate) during gamete formation, and
then unite at random, one from each parent, at fertilization.
• Mendel’s law of Independent Assortment: The alleles
of different genes assort independently of each other.
 Genetics explains the mechanisms
that determine the inheritance of traits

Genes underlie the formation of every heritable trait,

e.g. cleft chin, hair loss, color of hair, skin, and eyes
• Some traits are causes by a single change
in a single gene, e.g. sickle-cell anemia
• Some traits are caused by complex interactions between
many genes, e.g. facial features
 Organization of genetic information in
cells
Chromosomes are organelles that package and
manage the storage, duplication, and
expression of DNA
Genomes are the entire collection of
chromosomes in each cell of an organism (24
kinds of chromosomes)
– The haploid human genome contains
approximately 3 billion base pairs of DNA
packaged into 23 chromosomes.
– Of course, most cells in the body (except for
female ova and male sperm) are diploid, with
23 pairs of chromosomes. That makes a total
of 6 billion base pairs of DNA per cell.
• Encodes 20,000 – 30,000 genes
• Human also have a small amount of DNA in
their mitochondria, which has also been
sequenced.
15
 Eukaryotic genome
• Each base pair is ~ 0.34 nanometers long (a
nanometer is 1/ 109 of a meter)
• Each diploid cell => contains ~ 2 meters of DNA
[(0.34 × 10-9) × (6 × 109)]
• Our body contains about >37 trillion cells, which
works out to 100 trillion meters of DNA per
human.
• Now, consider the fact that the Sun is 150 billion
meters from Earth. We enough DNA to go from
here to the Sun and back more than 300 times!
– It needs to squeeze into 5-10 μm nucleus reducing
its length as much as 10,000 fold
• How is this possible?
• This is accomplished by the packing of linear
DNA molecules into chromatin (DNA with its
associated proteins).
 DNA/RNA?
• Genes are made of nucleic acids
• Nucleic acids are made of building blocks called
nucleotides
• Nucleotides have three components
– Sugar molecule (ribose or deoxyribose)
– Phosphate molecule
– Nitrogen-containing molecule (adenine, guanine,
cytosine, thymine, uracil)
• RNA is ribonucleic acid
• DNA is deoxyribonucleic acid
 The Relationship Between Genes and Traits

• Most genes encode polypeptides that are units within

functional proteins.

• Gene expression at the

molecular level involves
transcription to produce
mRNA and translation to produce
a polypeptide.
 The Relationship Between Genes and Traits

• Genetics, which governs an organism’s

traits, spans the molecular, cellular,
organism, and population levels.
• Genetic variation underlies variation in
traits.
• In addition, the environment also plays a
key role in genetic variation.
The biological information in DNA generates
an enormous diversity of living organisms

21
 Many genes have similar functions
in different organisms

Comparison of gene products in different organisms can

reveal identical and similar amino acid sequences
e.g. cytochrome C protein from six species
 A gene from one organism can functionally
replace a gene in another organism

Example: Pax6 gene is

required for eye
development in insects,
mice, and humans

Expression of human Pax6

gene in Drosophila can
induce eye development
 Two critical functions of DNA
1. Replication – necessary to ensure that genome is
replicated each cell division and each generation -
heredity

2. Code for proteins (and functional RNAs):

– gene transcription → RNA
– translation – nucleotide sequence of mRNA
specifies amino acid sequence of a polypeptide.
• transcription may also generate untranslated RNAs that have
functions (eg. rRNA, tRNA, miRNA).
•
 The amino acid sequence determines
the three-dimensional shape of the protein

Chemical formulas for two Three-dimensional shapes

amino acids of two proteins

Figure 1.5a Figure 1.5c

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1
26
 Proteins
• make up most of the mass of a cell
• regulate all cellular processes directly or indirectly
• enzymes involved in energy utilization, energy storage.
• enzymes for biosynthesis or breakdown of other
macromolecules (including DNA).
• proteins form scaffolds to hold other proteins and
macromolecules in place – to organize the cell.
• proteins regulate transport into and out of cells and
signaling between cells.
• motor proteins and other proteins regulate intracellular
transport.
 Molecular Diagnosis

Molecular diagnosis of human disorders is the detection of the

various disease-causing variants in DNA and /or RNA samples

Molecular Diagnostics
• Is the use of molecular biology techniques to increase the
scientific knowledge of the natural history of a certain
diseases, identify individuals who are at risk for developing
specific diseases, and make diagnosis of human disorders
• -Advance in the understanding of the structure and
chemistry of nucleic acids have facilitated the development
of technologies that can be employed effectively in
molecular diagnostics
 Cytogenetics
- Cytogenetics: is the study of the structure, and function of
chromosomes (material of inheritance in the cell nucleus),
chromosomal behavior during somatic cell division in growth and
development (mitosis) and germ cell division in reproduction
(meiosis), chromosomal influence on the phenotype and the
factors that cause chromosomal changes (Hare & Singh, 1979)

- Human cytogenetics is concerned with how these process may

go wrong, because change in number or in structures of certain
chromosomes(s) can cause diseases
 Problem solving

• Genetic diseases

What else?!
Genetic variation (at DNA or RNA level) ➔ the clinical
phenotype

• There are lots of different mutations/

variations that can occur in our DNA.
• Large-scale mutations/ variations
• Small- scale mutations/ variations
Suggested textbook:
New Clinical Genetics, fourth edition Paperback – December 15, 2020, by Andrew Read
(Author), Dian Donnai (Author). ISBN-10 : 1911510703 ISBN-13 : 978-1911510703