STRUCTURE OF DNA

AND RNA, GENES,

CHROMOSOMES
Heritable traits are passed down to offspring through genes
Structure of DNA and RNA

The structure of DNA allows efficient storage of

genetic information

• There is 2m of DNA in each human cell, however the most cells in the human body have a
diameter of 10 μm
• This DNA is divided in chromosomes and coiled around proteins called histones so that it can
be efficiently stored in each cell's nucleus
• The human genome project which has decoded the case sequence for the whole 2m of the
human genome requires a data warehouse (pictured) to store the information electronically
• This should give a good idea of just how efficient DNA is at storing information and why
it needs to be so
 THE
STRUCTUR
E OF DNA

The Structure of DN
A
 NUCLEIC ACIDS
◦ DNA is found in the nucleus with small amounts in mitochondria
and chloroplasts
◦ RNA is found throughout the cell
◦ Nucleic acids are polynucleotides
◦ Nucleoside = base + sugar
◦ Nucleotide = nucleoside + phosphate
 Present in all cells and virtually restricted to
the nucleus

The amount of DNA in somatic cells (body

cells) of any given species is constant
NUCLEIC (like the number of chromosomes)

ACIDS – DNA The DNA content of gametes (sex cells) is half

that of somatic cells

In polyploids DNA content increases by a

proportional factor
The nucleic acids DNA and RNA are polymers of nucleotides

A nucleotide: a single unit of a nucleic acid

Nucleic acids are very large molecules

that are constructed by linking
together nucleotides to form a
polymer

There are two types of nucleic acid: DNA and RNA

The nucleic acids DNA and RNA are polymers of nucleotides

A nucleotide: a single unit of a nucleic acid

• Acidic
• Negatively charged

• Contains nitrogen
• Has one or two rings in its
structure

covalent bond

• Five carbon atoms = a pentose sugar

• If the sugar is Deoxyribose the polymer is
Deoxyribose Nucleic Acid (DNA)
• If the sugar Ribose the polymer is Ribose
covalent bond
Nucleic Acid (RNA)
NUCLEIC ACIDS –
STRUCTURE
◦ Ribose – RNA / Deoxyribose - DNA
NUCLEIC ACIDS –
STRUCTURE
 NUCLEIC ACIDS –
NITROGENOUS BASES
NUCLEIC ACIDS –
STRUCTURE
◦ The nucleotides are all orientated in the
same direction
◦ The phosphate group joins the 3rd Carbon of
one sugar to the 5th Carbon of the next in
line
◦ The bases are attached to the 1st Carbon
◦ The order of the bases make the code for
amino acids
BASE PAIRS
DOUBLE
HELIX
 DNA STRUCTURE
◦ Each strand of DNA has a “direction”
- at one end, the terminal carbon atom in the backbone is the 5’ carbon atom of the terminal sugar
- at the other end, the terminal carbon atom is the 3’ carbon atom of the terminal sugar
◦ Chains are anti-parallel (i.e in opposite directions)
◦ Diameter and periodicity are consistent
◦ 2.0 nm
◦ 10 bases/ turn
◦ 3.4 nm/ turn
◦ Width consistent because of pyrimidine-purine pairing
DNA FORMS
 G-C CONTENT
◦ A-DNA conformation is favored when DNA is dehydrated
◦ B-DNA is the conformation normally found inside cells
◦ Z-DNA conformation is favored in certain GC-rich sequences\

◦ A=T, G=C, but AT≠GC

◦ Generally, GC~50%, but variable in different species

◦ Higher number of GC base pairs means more stable DNA - the strands don’t separate
as easily
The nucleic acids
DNA and RNA
are polymers of
nucleotides
The nucleic acids DNA and RNA are polymers of nucleotides

What is the relevance of this coffee cup to this topic?

http://lucasmind.tumblr.com
The nucleic acids DNA and RNA are polymers of nucleotides

There are four nitrogenous bases in DNA:

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

RNA Shares the same bases except that Uracil (U) replaces Thymine
The nucleic acids DNA and RNA are polymers of nucleotides

• Nucleotides are linked into a single strand via a

condensation reaction
• Bonds are formed between the phosphate of
one nucleotide and the pentose sugar of the
next
• The phosphate group (attached to the 5'-C of
the sugar) joins with the hydroxyl (OH) group
attached to the 3'-C of the sugar
• This results in a phosphodiester bond between
the two nucleotides and the formation of a
water molecule
• Successive condensation reactions between
nucleotides results in the formation of a long
single strand
DNA differs from RNA in the number of strands present, the base composition and the type of
pentose

RNA DNA
Adenine (A) Adenine (A)
Guanine (G) Guanine (G)
Bases Uracil (U) Thymine (T)
Cytosine (C) Cytosine (C)

Ribose Deoxyribose

Sugar

Single stranded, and often, Two anti-parallel,

but not always, linear in complementary strands
shape form a double helix
Number of strands
DNA is a double helix made of two antiparallel strands of nucleotides linked by hydrogen bonding
between complementary base pairs
DNA is a double helix made of two antiparallel strands of nucleotides linked by hydrogen bonding
between complementary base pairs
DNA is a double helix made of two antiparallel strands of nucleotides linked by hydrogen bonding
between complementary base pairs
DNA is a double helix made of two antiparallel strands of nucleotides linked by hydrogen bonding
between complementary base pairs

In Summary:
• Each polynucleotide chain (strand) consists of a chain of nucleotides bonded
covalently

• Two polynucleotide chains of DNA are held together by hydrogen bonds between
complementary base pairs:
Adenine pairs with thymine (A=T) via two hydrogen bonds
Guanine pairs with cytosine (G=C) via three hydrogen bonds

• In order for bases to be facing each other and thus able to pair, the two strands must
run in opposite directions (i.e. they are anti-parallel)

• As the polynucleotide chain lengthens, the atoms that make up the molecule will
arrange themselves in an optimal energy configuration
• This position of least resistance results in the double-stranded DNA twisting to form
a double helix with approximately 10 - 15 bases per twist
Crick and Watson’s elucidation of the structure of DNA using model making

Watson and Crick gained Nobel prizes for their discovery

It should be remembered that their success was based

on the evidence they gained from the work of others
In particular the work of Rosalind Franklin and Maurice
Wilkins, who were using X-ray diffraction was critical to
their success

Find out more about the discovery of DNA:

http://www.nobelprize.org/educational/medicine/dna_double_helix/readmore.html

http://scarc.library.oregonstate.edu/coll/nonspcoll/catalogu
e/picture-dnamodel-900w.jpg

http://youtu.be/sf0YXnAFBs8
◦ RNA – mainly involved in the process of protein synthesis under
the direction of DNA
◦ RNA is usually single-stranded and is made of ribonucleotides that
are linked by phosphodiester bonds
◦ A ribonucleotide in the RNA chain contains ribose (the pentose
sugar), one of the four nitrogenous bases (A, U, G, and C), and the
phosphate group

◦ There are major types of RNA:

◦ messenger RNA (mRNA)
◦ ribosomal RNA (rRNA)
◦ transfer RNA (tRNA)
RNA TYPES
RNA
◦ Types
- mRNA
- tRNA
- rRNA
- snRNA
- siRNA
◦ Messenger RNA (mRNA) carries the message from DNA,
which controls all the cellular activities in a cell
◦ The mRNA is read in sets of three bases known as codons
◦ Each codon codes for a single amino acid
◦ In this way, the mRNA is read, and the protein product is made
mRNA
◦ Information on the order of amino acids in the
protein
◦ Short half-life
◦ Around 4% of total RNA in the cell
◦ Immediately after the synthesis of the first two
ribonucleotides in the pre-mRNA, a cap at the 5 'end
is added – 7-methylguanosine connected through 5’-
5’ tri-phosphate bond
◦ Secures the mRNA end from 5’-exonucleases
◦ PolyA tail on 3’ end
mRNA
◦ Splicing – cutting out non-coding introns
◦ snRNPs – small nuclear ribonucleoproteins
◦ U-rich RNA

◦ Editing of mRNA – chemical modifications can

lead to changes in the coding properties of the
transcript, leading to changes in the amino acid
sequence of the encoded protein
◦ Ribosomal RNA (rRNA) is a major constituent of ribosomes
on which the mRNA binds
◦ The rRNA ensures the proper alignment of the mRNA and the
ribosomes
◦ The rRNA of the ribosome also has an enzymatic activity (peptidyl
transferase) and catalyzes the formation of the peptide bonds
between two aligned amino acids
◦ Transfer RNA (tRNA) is one of the smallest of the four types
of RNA, usually 70–90 nucleotides long
◦ It carries the correct amino acid to the site of protein synthesis
◦ It is the base pairing between the tRNA and mRNA that allows for
the correct amino acid to be inserted in the polypeptide chain

◦ microRNAs are the smallest RNA molecules, and their role

involves the regulation of gene expression by interfering with the
expression of certain mRNA messages
 A

tRNA B E

C
 tRNA
◦ A – acceptor arm – paired 5’ & 3’ ends of tRNA. CCA sequence at the end as an amino acid binding site
◦ B – DHU arm (D loop) – contains dihydrouracil – unique amino acid
◦ C – anticodon arm – recognition and binding to mRNA
◦ D – variate loop – only in some tRNAs
◦ E – TΨC loop – contains pseudo uracil
◦ tRNA genes appear in multiple copies
◦ There are round 40 different tRNAs
◦ Even though the RNA is single stranded, most RNA types show
extensive intramolecular base pairing between complementary
sequences, creating a predictable three-dimensional structure
essential for their function

◦ Information flow in an organism takes place from DNA to RNA to

protein
◦ DNA dictates the structure of mRNA in a process known as transcription, and
RNA dictates the structure of protein in a process known as translation  the
Central Dogma of Life, which holds true for all organisms
GENE
EXPRESSIO
N
◦ Central dogma of genetics:
A gene is a heritable factor that consists of a length of DNA and
influences a specific characteristic

• Genetics (from ‘genesis’) is the area of Biology

concerned with how information in organisms is
passed from parents to offspring / progeny
• 19th century scientists showed that there were
factors within organisms that determined their
characteristics and that these factors were
heritable
• The word gene was used to describe these
factors
• 20th century scientists showed that these genes
were made up of DNA
– Human cells contain 46 DNA molecules
(chromosomes) with ~23,000 genes

• Today it is understood that genes are segments of

a DNA molecule that influence or directly code for
specific traits
A gene is a heritable factor that consists of a length of DNA and
influences a specific characteristic
Comparison of the number of genes in humans with other species
A gene occupies a specific position (locus) on one type of chromosome

• Genes are distributed amongst an organisms chromosomes

• The location of a gene on a chromosome is called the locus of the gene
• All members of a species have the same chromosome number with the
same genes in the same loci along their chromosomes
What is a gene?
◦ What is a gene?
A gene occupies a specific position (locus) on one type of chromosome
The various specific forms of a gene are alleles

• Alleles are alternative versions of the same

gene. They occupy the same position (locus) on
one type of chromosome
• Mendel first observed and names ‘alleles’ in his
study of pea plant traits
• Most animals and plants have 2 alleles for each
gene (often one ‘dominant’ and one ‘recessive’)
• Some genes, like one for fur color in mice or ABO
blood type in humans, have more than 2 alleles
(aka ‘Multiple Alleles’)
Alleles differ from each other by one or a few bases only

• A gene consists of a length of DNA that

can be hundreds or thousands of bases
in length

• Alleles of a gene often differ only very

slightly in their base sequence
(sometimes by just 1-2 DNA letters, i.e.
one allele contains an Adenine where
the other has a Cytosine)

• These base differences are called

Single Nucleotide Polymorphisms
(SNPs, or ‘snips’)
Use of a database to determine differences in the base sequence of a
gene in two species

• One outcome of Human Genome Project is fast, computer based

methods of gene sequencing
• Web-based programs like GenBank and BLAST allow for the easy
comparison of nucleotide sequences in genes that are shared between
different species
• Based on the differences / similarities, timelines of evolutionary
relationships can be deduced
New alleles are formed by mutation
New alleles are formed by mutation

• Frameshift mutations are due to extra letters inserted or deleted

• This changes the entire reading frame of the mRNA codons and can have
massive effects for protein production
• Mutations that develop in body cells are eliminated when the
individual organism dies
• Mutations in gametes (sex cells) are passed on to offspring and can be
causes of genetic disease (sperm cells have a higher rate of mutation
than egg cells…)
• Human mutation rate is ~100-200 mutations per generation
The causes of sickle cell anemia, including a base substitution mutation, a
change to the base sequence of mRNA transcribed from it, and a change to the
sequence of a polypeptide in hemoglobin.
The causes of sickle cell anemia, including a base substitution mutation, a
change to the base sequence of mRNA transcribed from it, and a change to the
sequence of a polypeptide in hemoglobin
The causes of sickle cell anemia, including a base substitution mutation, a
change to the base sequence of mRNA transcribed from it, and a change to the
sequence of a polypeptide in hemoglobin
The causes of sickle cell anemia, including a base substitution mutation, a
change to the base sequence of mRNA transcribed from it, and a change to the
sequence of a polypeptide in hemoglobin
The causes of sickle cell anemia, including a base substitution mutation, a
change to the base sequence of mRNA transcribed from it, and a change to the
sequence of a polypeptide in hemoglobin
The causes of sickle cell anemia, including a base substitution mutation, a
change to the base sequence of mRNA transcribed from it, and a change to the
sequence of a polypeptide in hemoglobin
The causes of sickle cell anemia, including a base substitution mutation, a
change to the base sequence of mRNA transcribed from it, and a change to the
sequence of a polypeptide in hemoglobin

https://www.hhmi.org/biointeractive/sickle-
cell-anemia
The causes of sickle cell anemia, including a base substitution mutation, a
change to the base sequence of mRNA transcribed from it, and a change to the
sequence of a polypeptide in hemoglobin.
The genome is the whole of the genetic information of an organism

Genome: the whole genetic information of an organism

In humans:
• 46 chromosomes in nucleus plus mitochondrial DNA*
In plants:
• Chromosomes in the nucleus plus DNA in the
mitochondria and chloroplasts*
In prokaryotes:
• Much smaller genome consisting of DNA in a circular
chromosome and any plasmids
The entire base sequence of human genes was sequenced in the
Human Genome Project

The Human Genome Project (HGP) began in 1990 and produced

a full copy of a human genome in 2003…
• All humans genomes vary due to SNPs, but 99.9% of the
genome is identical among all humans
• Public / private competition and collaboration drove
incredibly rapid biotech research and development
• HGP produced a vast set of data in the form of the ~3.2 billion
base letter sequence of human DNA
• Scientists are still in the process of decoding these
sequences to ID specific genes
• ~23,000 genes were identified (much fewer than
predicted!)
• Discovered much of the genome is NOT transcribed
• Highly-repetitive sequences originally-called “junk DNA”
but now recognized as having a number of key functions
How to sequence the human genome -
Mark J. Kiel
◦ How to sequence the human genome - Mark J. Kiel
Chromosomes
Chromosomes carry genes in a linear
sequence that is shared by members of a
species

The Asian rice (Oryza sativa) genome can be seen illustrated above. Rice
possesses up 63,000 genes divided up between 12 chromosomes.

Below is a map of part of the first chromosome showing the gene loci present on it. Although different
varieties (estimated 40,000 worldwide) will possess different alleles for genes, all individuals will share the
same twelve chromosomes and the alleles of each variety will occur at the same position on same
chromosome, i.e. at the same gene loci.
What is a Chromosome?
◦ What is a Chromosome?
CELL STRUCTURE
◦ Each cell has four common components:
1. Plasma membrane
2. Region containing DNA
3. Cytoplasm
4. Biochemical molecules &
biochemical pathways
NUCLEUS
ENDOPLASMIC
RETICULUM
RIBOSOMES
MITOCHONDRIA
HUMAN CHROMOSOMES
STRUCTURE
◦ Eucaryotic chromosomes are visible
only during cell division
◦ Types:
- Metacentric
- Submetacentric
- Acrocentric
- Telocentric
Chromosome Anatomy
Replicated
centromere

p
short arm

q
long
arm

Submetacentric Metacentric Acrocentric Telocentric

◦ Chromatin
◦ Nucleosomes
◦ Histones with wrapped DNA
◦Active (euchromatin) and non-
active (heterochromatin) chromatin
- Barr bodies
◦ Constitutive chromatin
Prokaryotes have one chromosome consisting of a circular DNA molecule
Some prokaryotes also have plasmids but eukaryotes do not
Prokaryotes have two types of DNA:
• single chromosome
• plasmids

The single prokaryotic chromosome is coiled up

and concentrated in the nucleoid region
Because there is only a single chromosome there
is only one copy of each gene

A copy of the chromosome is made just

before cell division (by binary fission)
Some prokaryotes also have plasmids but eukaryotes do not

Prokaryote bacteria may have plasmids, but these structures are not found in
eukaryotes.*

Features of Plasmids:
• Naked DNA - not associated with histone
proteins
• Small circular rings of DNA
• Not responsible for normal life processes –
these are controlled by the nucleoid chromosome
• Commonly contain survival characteristics, e.g. antibiotic resistance
• Can be passed between Prokaryotes
• Can be incorporated into the nucleoid chromosome

n.b. Plasmid characteristics mean that Scientists have

found them useful in genetic engineering
Plasmids can be used to transfer genes into bacteria

*Scientists have found plasmids in archea and eukaryota, but very rarely
Cairns’ technique for measuring the length of DNA molecules by autoradiography
Nature of Science: Developments in research follow improvements in techniques - autoradiography was
used to establish the length of DNA molecules in chromosomes

John Cairns produced images of DNA molecules from Escherichia coli (E.coli)
• E. coli was grown with thymine containing a radioactive
isotope of hydrogen (the DNA was labelled)
• The E. coli cells were broken by enzymes to release the
cell contents
• The cell contents were applied to a photographic
emulsion and placed in the dark (for two months)
• The radioactive isotopes reacted with the emulsion
(similarly to light does)
• Dark areas on the photographic emulsion indicated the
presence of DNA
• The images showed that E. coli possesses a single
circular chromosome which is 1,100 μm long (E. coli
cells have a length of only 2 μm)
• Cairns images also provided evidence to support the Cairn's Technique
theory of semi-conservative replication
n.b. The insights and improvements in theory would not have been possible without the
development and use of autoradiography (exposure of photographic emulsion by
radioactive isotopes)
 Eukaryote chromosomes are linear DNA molecules associated with histone proteins
Linear strands of DNA held in a helix

Eukaryotic chromosomes may be up to 85mm in

length
To fit such a length of DNA into a nucleus with a
diameter of 10 μm it has to be coiled in a
predictable fashion that still allows for processes,
such as replication and protein synthesis, to
occur
Nucleosomes are formed by wrapping DNA
around histone proteins

n.b. Prokaryotic DNA is, like eukaryotic DNA, supercoiled, but

differently: Prokaryotic DNA may be associated with
proteins, but it is not organised by histones and is therefore
sometimes referred as being ‘naked’.

http://en.wikipedia.org/wiki/File:DNA_to_Chromatin_Formation.jpg
In a eukaryote species there are different chromosomes that carry different genes

Eukaryotes possess multiple chromosomes

All individuals of a species possess the same
chromosomes, with the same gene loci
-- all humans have 23 pairs
Chromosomes can vary by:
• Length – the number of base pairs in the DNA molecule
• Position of the centromere
• Genes occur at a specific locus (location), i.e. it is always
found at the same position on the same chromosome (the
locus and genes possessed vary between species)

https://public.ornl.gov/site/gallery/originals/
Use of databases to identify the locus of a human gene and its polypeptide product

Use the online database (http://www.genecards.org/) to search for the genes

and the loci responsible for synthesizing the following polypeptides:

• Rhodopsin
• 3 different types of Collagen
• Insulin
• One other protein of your choice

n.b. the list of polypeptides reflects the examples you were required to learn for 2.4.A1
The number of chromosomes is a characteristic feature of members of a species

The chromosome number is an important characteristic of the species

Organisms with different numbers of

chromosomes are unlikely to be able to
interbreed successfully

Chromosomes can fuse or split during

evolution – these are rare events and
chromosome numbers tend to stay the
same for millions of years

The number of chromosomes possessed by a

species is known as the N number, for example
humans have 23 different chromosomes

https://commons.wikimedia.org/wiki/File:NHGRI_human_male_karyotype.png
 Diploid nuclei have pairs of homologous chromosomes
Haploid nuclei have one chromosome of each pair

A diploid nucleus has two of each chromosome (2N)

Therefore, diploid nuclei have two copies of every gene, apart from the genes on the sex chromosomes
For example, the diploid nuclei in humans contain 46 chromosomes

The fertilized egg cell (zygote)

therefore is a diploid (2N) cell
containing two of each
chromosome

Gametes are the sex cells that fuse

together during sexual reproduction
Gametes have haploid nuclei, so in A haploid nucleus has one of
humans both egg and sperm cells each chromosome (N)
contain 23 chromosomes Haploid nuclei in humans have 23
different chromosomes

n.b. Diploid nuclei are less susceptible to genetic diseases: have two copies of a
gene means organisms are more likely to possess at least one healthy copy
http://www.biologycorner.com/resources/diploid_life_cycle.gif
Comparison of diploid chromosome numbers of Homo sapiens, Pan troglodytes, Canis familiaris, Oryza
sativa, Parascaris equorum

Humans (Homo sapiens) 46

46 is the number of diploid

chromosomes in each human cell

https://upload.wikimedia.org/wikipedia/commons/f/f6/Usain_Bolt_100_m_Daegu_2011.jpg
Comparison of diploid chromosome numbers of Homo sapiens, Pan troglodytes, Canis familiaris, Oryza
sativa, Parascaris equorum

Asian rice (Oryza sativa)

Equine roundworm (Parascaris equorum)

http://pic20.picturetrail.com/VOL176/4853602/20795519/357799225.jpg
How many diploid
chromosomes does each
species possess?
https://commons.wikimedia.org/wiki/File:Hinohikari.jpg

Domestic Dog (Canis familiaris)

Chimpanzee (Pan troglodytes)

https://commons.wikimedia.org/wiki/File:Dog_%28Canis_lupus_fa https://commons.wikimedia.org/wiki/File:Pan_troglodytes_Sweetwaters_Chim
miliaris%29_%281%29.jpg panzee_Sanctuary,_Kenya.jpg
Comparison of diploid chromosome numbers of Homo sapiens, Pan troglodytes, Canis familiaris, Oryza
sativa, Parascaris equorum.

Asian rice (Oryza sativa) 24

2 Equine roundworm (Parascaris equorum)

http://pic20.picturetrail.com/VOL176/4853602/20795519/357799225.jpg
How many diploid
chromosomes does each
species possess?
https://commons.wikimedia.org/wiki/File:Hinohikari.jpg

Domestic Dog (Canis familiaris) 78

48 Chimpanzee (Pan troglodytes)

https://commons.wikimedia.org/wiki/File:Dog_%28Canis_lupus_fa https://commons.wikimedia.org/wiki/File:Pan_troglodytes_Sweetwaters_Chim
miliaris%29_%281%29.jpg panzee_Sanctuary,_Kenya.jpg
Homologous chromosomes carry the same sequence of genes but not necessarily the same alleles of
those genes
Sex is determined by sex chromosomes and autosomes are chromosomes that do not determine sex

Sex Determination: It’s all about X and Y…

Humans have 23 pairs of chromosomes in
diploid somatic cells (n=2)

22 pairs of these are autosomes, which are

homologous pairs

One pair is the sex chromosomes.

XX gives the female gender, XY gives male

Karyotype of a human male, showing X and Y chromosomes:

http://en.wikipedia.org/wiki/Karyotype
SRY
The X chromosome is much larger than the Y
X carries many genes in the non-homologous
region which are not present on Y

The presence and expression of the SRY gene on

Y leads to male development

Chromosome images from Wikipedia:

http://en.wikipedia.org/wiki/Y_chromosome
Sex is determined by sex chromosomes and autosomes are chromosomes that do not determine sex.

Chromosome pairs segregate in meiosis

Females (XX) produce only eggs containing the X

chromosome

Males (XY) produce sperm which can contain

either X or Y chromosomes

Segregation of the sex chromosomes in meiosis.

SRY gene determines maleness.
gametes X Y
X XX XY

X XX XY
Therefore, there is an even chance*
of the offspring being male or female
Comparison of genome size in T2 phage, Escherichia coli, Drosophila melanogaster, Homo
sapiens and Paris japonica

Humans (Homo sapiens)

3.2 billion base pairs

Genome size is the total number of

DNA base pairs in one copy of a
haploid genome

https://upload.wikimedia.org/wikipedia/commons/f/f6/Usain_Bolt_100_m_Daegu_2011.jpg
Comparison of genome size in T2 phage, Escherichia coli, Drosophila melanogaster, Homo
sapiens and Paris japonica

T2 phage
Canopy plant (Paris japonica)

Escherichia coli

https://s-media-cache-ak0.pinimg.com/736x/2d/0e/3e/2d0e3ea8d
df652f25a5f2c3b1050af79.jpg

n.b. T2 phage (orange) is a virus that attacks E. Coli

bacterium (green and white).

What is the genome size of

each species?

Fruit fly (Drosophila melanogaster)

https://commons.wikimedia.org/wiki/File:Dr
osophila_melanogaster_-_side_%28aka%29.j
pg

https://commons.wikimedia.org/wiki/File:Paris_japonica_Kinugasasou_in_Hakusan_2003_7_27.jpg
Comparison of genome size in T2 phage, Escherichia coli, Drosophila melanogaster, Homo
sapiens and Paris japonica.

T2 phage
Canopy plant (Paris japonica)
164 thousand base pairs
150 billion base pairs

Escherichia coli
4.6 million base pairs

https://s-media-cache-ak0.pinimg.com/736x/2d/0e/3e/2d0e3ea8d
df652f25a5f2c3b1050af79.jpg

n.b. T2 phage (orange) is a virus that attacks E. Coli

bacterium (green and white).

What is the genome size of

each species?

Fruit fly (Drosophila melanogaster)

https://commons.wikimedia.org/wiki/File:Dr
140 million base pairs
osophila_melanogaster_-_side_%28aka%29.j
pg

https://commons.wikimedia.org/wiki/File:Paris_japonica_Kinugasasou_in_Hakusan_2003_7_27.jpg
A karyogram shows the chromosomes of an organism in homologous pairs of decreasing length

Karyogram is a diagram or photograph of the chromosomes present in a nucleus (of

a eukaryote cell) arranged in homologous pairs of decreasing length.

The chromosomes are visible in cells that are undergoing

mitosis – most clearly in metaphase

Stains used to make the chromosomes visible also give each

chromosome a distinctive banding pattern

A micrograph are taken, and the chromosomes are arranged according to their
size, shape and banding pattern
They are arranged by size, starting with the longest pair and ending with the
smallest

https://commons.wikimedia.org/wiki/File:NHGRI_human_male_karyotype.png
A karyogram shows the chromosomes of an organism in homologous pairs of decreasing length

Karyotype is a property of the cell described by the number and type of

chromosomes present in the nucleus (of a eukaryote cell)

a Karyogram is a diagram
that shows, or can be used to
determine, the karyotype

http://learn.genetics.utah.edu/content/chromosomes/karyotype/
Description of methods used to obtain cells for karyotype analysis e.g. chorionic villus sampling and amniocentesis and the
associated risks. AND 3.3.A2 Studies showing age of parents influences chances of non-disjunction

The risk of a child having a

trisomy such as Down
Syndrome increases greatly in
older mothers

It is often advisable for

mothers in a high-risk
category to choose to have a
prenatal (before birth) test

Amniocentesis or chorionic
villus samples can be taken
and from them a karyotype
can be constructed

Data from a positive test can

be used to decide the best
course of action, which at
times be to abort the fetus

https://commons.wikimedia.org/wiki/File:Down_Syndrome_Risk_By_Age.png
Description of methods used to obtain cells for karyotype analysis e.g. chorionic villus sampling and
amniocentesis and the associated risks
Description of methods used to obtain cells for karyotype analysis e.g. chorionic villus sampling and
amniocentesis and the associated risks.

Can be carried out in the 16th week of the pregnancy with around
a 1% chance of a miscarriage

http://www.medindia.net/animation/amniocentesis.asp
Description of methods used to obtain cells for karyotype analysis e.g. chorionic villus sampling and
amniocentesis and the associated risks.

Can be carried out in the 11th week of the

pregnancy with around a 2% chance of a
miscarriage
These tests may be necessary in pregnant
women who:
◦ Have received a high-risk screening result from a screening test ( FTS / Quadruple /Triple
Test) for Down syndrome or similar problems
◦ Advanced maternal age
◦ Have had a family or previous pregnancy history of a genetic disorder
◦ Where a fetal structural abnormality is found
The test
◦ Amniocentesis is a procedure in which a small amount of the amniotic fluid surrounding
the baby in the womb is removed by passing a fine needle through the mother’s abdomen
◦ Amniocentesis is performed after 15 weeks of pregnancy

◦ CVS is a procedure in which a small number of fetal tissues from the placenta in the womb is
removed by passing a fine needle through the mother’s abdomen
◦ CVS is performed at 11-13 weeks of pregnancy
The risk
◦ Most women say that having amniocentesis / CVS is uncomfortable rather than painful, a bit like
a period pain
◦ Women describe a sharp stinging feeling when the needle goes in and a feeling of pressure when
the needle comes out
◦ You may notice some cramping for a few hours afterwards -- This is normal.
◦ Experience of any unusual symptoms after the test, such as feeling shivery (as if you have flu),
fluid loss, bleeding or contractions requires advice immediately
◦ Every pregnancy carries a risk of miscarriage
◦ Amniocentesis / CVS involves putting a needle through the wall of the womb. It may sometimes cause a
miscarriage due to injury or infection in the womb
◦ The additional overall risk of miscarriage is approximately 1%
The Interpretation
◦ For most women the laboratory test will give a definite ‘yes’ or ‘no’ answer
◦ Many women who have amniocentesis /CVS will have a ‘normal’ result -- their baby will be
born without the disorder(s) the test was looking for
◦ Some women will be informed that the baby has the disorder that the test was looking for
◦ If the results are abnormal, these will be discussed fully
◦ For the majority of disorders, there is no treatment or cure so there are options to be
considered:
◦ 1. Terminate this pregnancy
◦ 2. Or continue with the pregnancy and use the information you have gained to help prepare for the
birth and aftercare of baby
The Procedure
◦ Both Amniocentesis and CVS are outpatient procedures and will not need admission
◦ In Amniocentesis, using an ultrasound probe for accurate guidance and to ensure a safe
distance from the baby, a fine needle is pushed into skin, through abdomen and womb, under a
local anaesthetic
◦ A small sample (15-20 mls) of the fluid surrounding the baby is removed using a syringe
◦ This fluid is amber/yellow colour but may sometimes be stained with blood
◦ The needle is then taken out and the baby’s heartbeat is checked on ultrasound
◦ The amniotic fluid, which contains some of the baby’s cells, is sent to the laboratory for
testing
The Procedure
◦ In CVS, a small amount of placental sample (Chorionic Villi) is removed using a syringe more
or less in the same way
◦ For a very small group women having Amniocentesis/CVS, not enough fluid/ chorionic tissues
can be taken and the needle may need to be re-inserted
◦ If blood group is Rh negative, the patient will be advised to have an injection of anti-D
immunoglobulin after the procedure to prevent from developing antibodies against the baby’s
blood cells
◦ After the procedure, the rest is required for at least half an hour before going home
Use of karyogram to deduce sex and diagnose Down syndrome in humans

Can you use a karyogram to determine sex and whether a person has Down
Syndrome?

Use the Biology Project activity to practice

your skills and understanding:
http://www.biology.arizona.edu/human_bio/activities/karyotypin
g/karyotyping.html

http://learn.genetics.utah.edu/content/disorders/chromosomal/down/
 Chromosomal Disorders Come in 2 Forms
1.0

O
Incidence among newborns (%)

v
e 1/154 40–50% of spontaneous abortions have
r chromosomal abnormalities
0.5 a
l 1/263
1/375
l 1/500
0.25 1/475
1/700
i 1/1600
0 n
c
All chromosomal Total X and Y Total Balanced Unbalanced
abnormalities
i Autosomes chromosomes
d
e
n Aneuploidy Structural
c Abnormalities
e
 CHROMOSOMAL
DISORDERS
NONDISJUNCTION
AND AUTOSOMAL
POLYPLOIDY
◦ Different number of chromosomes comes from errors during meiosis
◦ Gametes with incorrect number of chromosomes produce organism with
same number of incorrect genetic material in all cells
◦ Improper mitosis results in somatic cells with different karyotypes
within one organism – a mosaic

◦ Ploidy – multiplication of genetic material: 23-haploid, 46-diploid,

69-triploid etc.
◦ Aneuploidy – multiplication or deletion of one or more
chromosomes:
- Monosomy
- Disomy
- Trisomy
◦ Most ploids are spontaneously aborted
◦ There are different diseases connected with aneuploids in humans
Aneuploidy
◦ Aneuploidy is the presence of an abnormal number of
chromosomes in a cell, for example a human cell having 45 or 47
chromosomes instead of the usual 46
 ANEUPLOIDY – DISEASES
Chromosome Number Appearance
Autosomy
Edwards syndrome 18 1:5000
Pateau syndrome 13 1:5000
Down syndrome 21 1:750
Sex chromosome
Turner syndrome XO 1:10000
Klinefelter syndrome XXY 1:2000
Triple X chromosome syndrome XXX 1:2000
RISK OF
ANEUPLOIDY
DEPENDING
ON AGE
 POLYPLOIDITY AND
EVOLUTION
◦ Autopolyploid – all genomes are identical or very similar and arise via genome duplication
within the same species
- Triploids are usually sterile – salmon / bananas

◦ Allopolyploid – contain two or more distinct genomes, and can arise via hybridization of two
different species concomitant with genome doubling

◦ Segmental allopolyploid – carry more than two partially differentiated genomes, which can
lead to the formation of both bivalents and multivalent during chromosome pairing
 POLYPLOIDITY AND
EVOLUTION
◦ Increased number of alleles of a given gene in a polyploid should allow the masking of deleterious recessive
mutations and thus insure against the loss of fitness
◦ Heterosis allows offspring to display transgressive performance compared with its progenitor species
◦ Duplicated gene copies can evolve to assume new or slightly varied functions
◦ In the new polyploid changes can lead to reduced, additive or transgressive states
◦ Polyploidization produces offspring that has the potential to be distinctly different from both of its parents
◦ These changes mostly concern plant evolution
 Chromosomal mutation – change in the
structure or number of chromosomes arising
spontaneously or under the influence of
mutagenic agents (eg ionizing radiation,
ultraviolet radiation, high temperature)

CHROMOSOMAL Numerical
ABERRATIONS

Structural
◦ Rearrangement: Bcr-Abl - chronic myeloid leukemia

◦ Rearrangement: Alk – lung cancer

Structural abnormalities
◦ Structural abnormalities are when part of an individual chromosome is missing,
extra, switched to another chromosome, or turned upside down
◦ Deletion - loss of the chromosome segment
◦ Deficiency - loss of the final segment of the chromosome
◦ Inversion - inversion of the chromosome fragment by 180 degrees
amplification of the chromosome segment
◦ Duplication - doubling the sections between nonhomogeneous chromosomes
◦ Translocation - separation of the chromosome arm
◦ Centromere crack - the chromosome arms combine to form a ring; usually
accompanied by the deletion of fragments located at the ends of the chromosome
◦ Chromosomal abnormalities can occur as an accident when the egg or the sperm
is formed or during the early developmental stages of the fetus
Aneuploidies Result from Nondisjunction
MEIOSIS
I Nondisjunction

MEIOSIS II
Nondisjunction

FERTILIZATION

aneuploid
Only 3 Autosomal Polyploidies Are Viable

Down Syndrome Edward syndrome Patau Syndrome

(Trisomy 21) (Trisomy 18) (Trisomy 13)
Trisomy 21 – Down Syndrome

Karyotype from a male patient with Down syndrome, showing 3 copies of chromosome 21
Trisomy 21 – Fluorescence in Situ Hybridization Analysis

Chromosome 21
Chromosome 21

Chromosome 21
Trisomy 21 – Whole Genome Chromosomal Microarray
Trisomy 21 – Whole Genome Sequencing
Trisomy 21 – Statistics
.1
2
• 1 in 850 children .1 At amniocentesis
are born with Down 1 At birth
Syndrome .1

Frequency of Down syndrome

0
• Much higher .09
incidence in .08
mothers over 35 .07
.05
.06
.04
• Only approximately
20% to 25% of .03
trisomy 21 .02
conceptuses .0
survive to birth. 1
0
0 20 25 30 35 40 45 50
Maternal age (years)
Trisomy 21 – Statistics
.1
2
• 1 in 850 children .1 At amniocentesis
are born with Down 1 At birth
Syndrome .1

Frequency of Down syndrome

0
• Much higher .09
incidence in .08
mothers over 35 .07
.05
.06
.04
• Only approximately
20% to 25% of .03
trisomy 21 .02
conceptions survive .0
until birth 1
0
0 20 25 30 35 40 45 50
Maternal age (years)
Trisomy 21 – Clinical
Diagnosis
Sparse hair Eyes
• Short, sparse lashes
• Brushfield spots Developmental
Small head delays of varying
with flat face degrees
Small, low-set ears

Hypotonic muscles

Dental anomalies,
arched palate,
protruding tongue

Broad, short
neck
Trisomy 21 – Clinical Diagnosis
Variations on Down Syndrome – Chromosomal Mosaicism

2% of Down syndrome patients are mosaic for trisomy 21.

Mosaicism
◦ Mosaicism occurs when a person has two or more genetically
different sets of cells in his or her body
◦ If those abnormal cells begin to outnumber the normal cells, it
can lead to disease that can be traced from the cellular level to
affected tissue, like skin, the brain, or other organs
Variations on Down Syndrome – Robertsonian Translocation

Lost short
arms

2 acrocentric Robertsonian
chromosomes translocation

4% of Down syndrome patients have 45 or 46 chromosomes

Robertsonian translocation
◦ Robertsonian translocation (ROB) is a chromosomal
abnormality wherein a certain type of a chromosome becomes
attached to another
◦ It is the most common form of chromosomal translocation in
humans, affecting 1 out of every 1,000 babies born
Variations on Down Syndrome – Partial Trisomy
Only 3 Autosomal Polyploidies Are Viable

Edward and Patau

Syndrome are much
less common and
have much more
deleterious effects

Down Syndrome Edward Syndrome Patau Syndrome

(Trisomy 21) (Trisomy 18) (Trisomy 13)
Structural Abnormalities Can Arise in Several Ways

Duplication Deletions Translocations

s

Results in haploinsufficiency or overexpression of one or more genes encoded in that region

Haploinsufficiency
◦ Haploinsufficiency in genetics describes a model of dominant
gene action in diploid organisms, in which a single copy of the
wild-type allele at a locus in heterozygous combination with a
variant allele is insufficient to produce the wild-type phenotype
◦ Haploinsufficiency may arise from a de novo or inherited loss-
of-function mutation in the variant allele, such that it yields little
or no gene product (often a protein)
Cri-du-chat Syndrome (5p Deletion Syndrome)
0
15.3
15.2
Speech 15.1
Cat cry 14
13.3
Mental retardation 13.2
Facial phenotype 10 13.
• Called Crie-du-chat due to the typical 1
Mental retardation
cat-like cry of affected children

• Terminal or interstitial deletion of the 20

short arm of chromosome 5 (5p)

Mental retardation

• Highly variable break points mean 30

variable expression

40
Cri-du-chat Syndrome (5p Deletion Syndrome)
0
15.3
15.2
Speech 15.1
Cat cry 14
13.3
Mental retardation 13.2
Facial phenotype 10 13.
1
Mental retardation

• Symptoms due to haploinsufficiency 20

• 90% due to de novo mutation Mental retardation

30

40
Cri-du-chat Syndrome

Hypertelorism – increased distance between two body parts

Cri-du-chat Syndrome

Epicanthus – skin fold covering the medial angle of the eye

Cri-du-chat Syndrome

Retrognathia
 Cri-du-chat Syndrome

Retrognathia – used to describe an unusual position of the mandible

Retro implies that there is deficient growth and 'gnathia' means about the jaws (particularly
mandible)
Cri-du-chat Syndrome

This individual with cri-du-chat syndrome is shown at 2, 4, 9, and 12 years of age

Translocations

• Quadrivalent
formation is necessary
to align homologous
segments during meiosis
I

• Formation of balanced
or
unbalanced gametes
Balanced Translocations

• 1 in 2000 newborns

• Generally no obvious
phenotypic effect

• Some involve direct

disruption of a gene
Segregation of Chromosomes with Inversions
Paracentric Pericentric

Segregation of inversions is generally uneventful

Recombination within the inverted segment can result in unbalanced gametes.

Autosomal Disorders Associated with Genomic
Imprinting

Prader- Angelman‘s
Willi syndrome
syndrome

Both result from microdeletions on chromosome 15

Autosomal Disorders Associated with Genomic Imprinting

• Genes are expressed in a parent of origin

specific manner
Genomic imprinting
◦ Genomic imprinting is an epigenetic phenomenon that causes
genes to be expressed or not, depending on whether they are
inherited from the mother or the father
◦ Genes can also be partially imprinted  Partial imprinting
occurs when alleles from both parents are differently expressed
rather than complete expression and complete suppression of one
parent's allele
Autosomal Disorders Associated with Genomic Imprinting
Chromosome 15 contains a genomically imprinted region

Genes are expressed only on the paternal (blue) and maternal (pink) chromosomes
Each region is hypermethylated (imprinted/ turned-off) on the opposing chromosome
Thus, a deletion in the expressed region results in PWS or AS
Prader-Willi Syndrome
Prader-Willi Syndrome results from a microdeletion of
paternal chromosome 15
1 in 15,000 live births

Paternal
Chromosom
e

Maternal
Chromosom
e
Prader-Willi Syndrome
Prader-Willi Syndrome results from a microdeletion of
paternal chromosome 15
1 in 15,000 live births

Paternal
Chromosom
e

Maternal
Chromosom Imprinted Region
e
Prader-Willi Syndrome
Prader-Willi Syndrome results from a microdeletion of
paternal chromosome 15
1 in 15,000 live births

Paternal
Chromosom Microdeletion
e

Maternal
Chromosom Imprinted Region
e
Prader-Willi Syndrome
Prader-Willi Syndrome results from a microdeletion of
paternal chromosome 15
1 in 15,000 live births

Paternal
Chromosom Microdeletion
e

Maternal
Chromosom Imprinted Region
e

No PWS Gene
expression = PWS
Prader-Willi Syndrome
Major Phenotypic Features
• Age of onset: Infancy

• Infantile feeding difficulties

• Childhood hyperphagia and

obesity

• Hypotonia

• Cognitive impairment

• Short stature

• Dysmorphism
Angelman Syndrome
Angelman Syndrome results from a microdeletion in
maternal chromosome 15

Paternal
Chromosom
e Imprinted
region

Maternal
Chromosom Microdeletion
e

No AS gene
expression = AS
Angelman Syndrome
Major Phenotypic Features
• Microcephaly

• Short stature

• Seizures

• Minimal speech

• Frequent smiling and laughing

• Developmental delays

• Severe intellectual disabilities

• Widely spaced teeth

Genomic Mechanisms of Prader-Willi and Angelman Syndromes

Mechanism Prader-Willi syndrome Angelman syndrome

15q11.2–q13 deletion 70% 70%

(paternal) (maternal)

Uniparental disomy 20–30% 7%

(maternal) (paternal)
Uniparental Disomy
Nondisjunction

Meiosis I Non-
disjunction

Meiosis II

Paternal ejected to Normal

rescue trisomy
Heterodisomy Isodisom
y
Single-gene Disorders
Pedigrees and Autosomal Patterns of
Inheritance
Single-gene Disorders
Victor A. McKusick’s

Mendelian inheritance in man

A classic that lists all known
single-gene disorders
Single gene disorders
◦ Single gene disorders are caused by DNA changes in one
particular gene, and often have predictable inheritance patterns
A Terminology Recap
The haplotype is A–B.

• Homologs
The locus 1
• Locus/loci genotype is
Aa.
• Heterozygous/homozygous

• Compound heterozygote

• This individual is
Genotype
heterozygous at
both locus A
• Haplotype and locus B.

• Phenotype
Compound heterozygote: 2 different mutant alleles, rather
than 1 wild-type and one mutant allele
 A Concept Recap: Pleiotropy
Blindness
Beta globin
gene mutation
(sickle cell
anemia) Pleiotropy
Liver failure

Multiple traits

Heart attack

Single gene
Pleiotropy
◦ Pleiotropy refers to the phenomenon in which a single locus
affects two or more apparently unrelated phenotypic traits and is
often identified as a single mutation that affects two or more
wild-type traits
A Concept Recap: Penetrance vs. Expressivity
BB x bb

Bb

Variable Variable Variable penetrance

penetrance expressivity and expressivity
Penetrance and expressivity
◦ Penetrance is the percentage of animals of a specific genotype
who express the phenotype associated with that underlying
genotype

◦ Expressivity refers to the degree that a particular genotype is

expressed as a phenotype within an individual
The Pedigree: A Graphical Representation of the Family
Tree
The Pedigree –
a Graphical
Representation of
the Family Tree
Patterns of Inheritance are Dependent Upon

• Autosome

• Sex chromosome

• Mitochondrial

• Dominant

• Recessive
Autosomal Recessive Inheritance
Carrier father Carrier mother
Autosomal recessive disease
occurs in individuals with 2
mutant alleles and no wild-
type allele

Loss-of-function
Mutations

Compensation

Mutant allele

Wild-type allele Unaffected Carrier Carrier son Affected

son daughter daughter
 3 Types of Mating Leads to Affected
Offspring
Carrier by affected Parent 2 genotype Risk for disease

R/r gametes

R r
¼
Parent 1 unaffected
genotype R R/R R/r (R/R), ½
R/r unaffected
gametes carriers
(R/r), ¼
affected
r R/r r/r (r/r)
 3 Types of Mating Leads to Affected Offspring
Carrier by affected Parent 2 genotype Risk for disease

r/r gametes

r r
Parent 1 ½
genotype R R/r R/r unaffected
R/r carriers
gametes (R/r),
½ affected
(r/r)
r r/r r/r
 3 Types of Mating Leads to Affected
Offspring
Carrier by affected Parent 2 genotype Risk for disease

r/r gametes

r r
Parent 1
genotype r r/r r/r All
r/r affected
gametes (r/r)

r r/r r/r
A Typical Autosomal Recessive Pedigree
Parents are carriers, apparent generation skip

About 1 in 4 offspring is affected

Male and female are affected equally
Cystic Fibrosis – a Relatively Common Autosomal Recessive
Disorder
Normal CFTR channel moves chloride
ions to the outside of the cell
Mutant CFTR channel does not move
chloride ions, causing sticky mucus to
build up on the outside of the cell

Outside cell Mucus

Inside cell

Chloride ions

1 child in 2.000 has CFTR mutation

1 in 23 people are silent carriers
On Occasion, Autosomal Recessive Disorders Are Sex-
influenced
Hereditary hemochromatosis is 5–10x more likely in males than females

Symptoms
• Enhanced absorption of dietary iron
• Causes iron overload
• Serious damage to the heart, liver, and pancreas
Affected Individuals Are Generally Compound
Heterozygotes

Alleles for recessive disorders are

uncommon so an affected individual is
usually a compound heterozygote
rather than being truly homozygous.

The exception is in consanguinity

Some Autosomal Recessive Disorders
• Sickle cell anemia

• Cystic fibrosis

• Albinism

• Phenylketonuria (PKU)

• Tay-Sachs disease
(hexosaminidase A deficiency)

• Hemochromatosis

• Glycogen storage deficiency

Some Autosomal Recessive Disorders
• Sickle cell anemia

• Cystic fibrosis

• Albinism

• Phenylketonuria (PKU)

• Tay-Sachs disease
(hexosaminidase A deficiency)

• Hemochromatosis

• Glycogen storage deficiency

Some Autosomal Recessive
Disorders
• Sickle cell anemia

• Cystic fibrosis

• Albinism

• Phenylketonuria (PKU)

• Tay-Sachs disease
(hexosaminidase A deficiency)

• Hemochromatosis

• Glycogen storage deficiency

Some Autosomal Recessive Disorders
• Sickle cell anemia

• Cystic fibrosis

• Albinism _ _

• Phenylketonuria (PKU) + 3
O2 H2O + 3

tetrahydro- dihydro-
• Tay-Sachs disease Phenylalanin biopterin biopterin Tyrosin
(hexosaminidase A deficiency) e e

• Hemochromatosis

• Glycogen storage deficiency

Some Autosomal Recessive Disorders
• Sickle cell anemia

• Cystic fibrosis

• Albinism

• Phenylketonuria (PKU)

• Tay-Sachs disease
(hexosaminidase A deficiency)

• Hemochromatosis

• Glycogen storage deficiency

Some Autosomal Recessive
Disorders
• Sickle cell anemia

• Cystic fibrosis

• Albinism

• Phenylketonuria (PKU)

• Tay-Sachs disease
(hexosaminidase A deficiency)

• Hemochromatosis

• Glycogen storage deficiency

Some Autosomal Recessive Disorders
• Sickle cell anemia

• Cystic fibrosis

• Albinism

• Phenylketonuria (PKU)

• Tay-Sachs disease
(hexosaminidase A deficiency)

• Hemochromatosis

• Glycogen storage deficiency

Some Autosomal Recessive Disorders

HINT:

Almost all diseases that show

up in childhood are AR

So think about learning the

shorter list of X-linked
recessive
Autosomal Dominant Inheritance
Heterozygote (affected) father Heterozygote (affected) mother

Mutant allele
Wild-type allele Unaffected Affected Affected Affected
son daughter son daughter

Autosomal dominant disease occurs in any individual that carries 1 deleterious allele.
 2 Types of Mating Leads to Affected
Offspring
Carrier by affected Parent 2 genotype Risk for disease

d/d gametes

d d
Parent 1
genotype D D/d D/d
½ affected (D/d), ½
D/d
unaffected (d/d)
gametes

d d/d d/d
 2 Types of Mating Leads to Affected
Offspring

Carrier by affected Parent 2 genotype Risk for disease

D/d gametes

D d
Strictly dominant
Parent 1 ¾ affected (D/D and D/d),
genotype D D/D D/d ¼ unaffected (d/d)
D/d Incompletely dominant
gametes ¼ severely affected
(D/D),
½ affected (D/d), ¼
d D/d d/d unaffected (d/d)
2 Types of Mating Leads to Affected Offspring
• Dominant conditions have a higher
incidence

• Polycystic kidney disease

occurs in 1 in 1,000 individuals in
the United States

• The incidence of familial

hypercholesterolemia is 1 in
100 for afrikaner populations in
South Africa
2 Types of Mating Leads to Affected Offspring
• Dominant conditions have a higher
incidence

• Polycystic kidney disease

occurs in 1 in 1,000 individuals in
the United States

• The incidence of familial

hypercholesterolemia is 1 in
100 for african populations in
South Africa
Pure Dominant Inheritance

Huntington’s disease exhibits pure dominant inheritance

Incompletely Dominant Inheritance

• Achondroplasia is an
incompletely dominant
skeletal disorder

• Short-limbed dwarfism

• Large head

• Mutations in the
fibroblast growth factor
receptor (FGFR3) gene
Incompletely Dominant Inheritance

• Achondroplasia is an
incompletely dominant
skeletal disorder

• Short-limbed dwarfism Parents were

heterozygous and
• Large head had much less
severe symptoms
• Mutations in the
The deceased
fibroblast growth factor
child was
receptor (FGFR3) gene
homozygous.
Inheritance Can Also be Sex Limited in Dominant Disorders
In male-limited precocious puberty, boys develop secondary sexual
characteristics. They undergo an adolescent growth spurt around 4 years old

Male-to-male transmission Transmission through carrier

shows that inheritance is females shows that inheritance
autosomal, not X-linked cannot be Y-linked
Understanding Inheritance Can Get Complicated

• Incomplete penetrance and

variable expressivity can
interfere with understanding the
inheritance of certain diseases

• Factors that must be taken into

account in genetic counseling Failure of penetrance
in mother and sister

Split-hand
deformity
Some Autosomal Dominant Disorders

• Familial Hypercholesterolemia
(LDL receptor deficiency)

• Huntington's disease

• Neurofibromatosis – 1

• Osteogenesis imperfecta

• Acute intermittent porphyria

• Adult polycystic kidney disease

Xanthomas, seen here on the knuckles, are often seen in patients with familial
hypercholesterolemia
Some Autosomal Dominant Disorders

• Familial Hypercholesterolemia
(LDL receptor deficiency)

• Huntington's disease

• Neurofibromatosis – 1

• Osteogenesis imperfecta

• Acute intermittent porphyria

• Adult polycystic kidney disease

Some Autosomal Dominant Disorders

• Familial Hypercholesterolemia
(LDL receptor deficiency)

• Huntington's disease

• Neurofibromatosis – 1

• Osteogenesis imperfecta

• Acute intermittent porphyria

• Adult polycystic kidney disease

Some Autosomal Dominant Disorders

• Familial Hypercholesterolemia
(LDL receptor deficiency)

• Huntington's disease

• Neurofibromatosis – 1

• Osteogenesis imperfecta

• Acute intermittent porphyria

• Adult polycystic kidney disease

Some Autosomal Dominant Disorders

• Familial Hypercholesterolemia
(LDL receptor deficiency)

• Huntington's disease

• Neurofibromatosis – 1

• Osteogenesis imperfecta

• Acute intermittent porphyria

• Adult polycystic kidney disease