Download Basic genetics: Directed-study File

Basic Concepts
in Human GENETICS
Pedro Amarante Andrade, PhD
LCSC06
BIOSCIENCES
FOR SPEECH AND LANGUAGE THERAPY
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READ THROUGH THE FOLLOWING
SLIDES
• You may find that you need more of an introduction to
the topic if this aspect of bioscience is totally new to
you. Therefore, you should read the chapters on
genetics in Atkinson & McHanwell or Tortora
• Some of the slides have notes attached, so you might
like to print off as ‘notes pages’ to assist you
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CHROMOSOME
• Made of DNA, protein,
and RNA;
• Single piece of coiled
DNA – contains genes,
regulatory elements and
other nucleotide
sequences
• Encodes most of all of the
organism’s genetic
information
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CHROMOSOME
• Are found in the nucleus of cells,
• All but the gametes contain 23 pairs (22 pairs of
autosomes and one pair of sex chromosomes)
• One chromosome in each pair comes from each parent
• The two chromosomes in a pair are typically
homologous i.e. contain the same genes, which control
the same traits
• Two alternative forms of the same gene are called
ALLELES
• One may be normal and the other abnormal
• One may be dominant, the other recessive
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CHROMOSOMAL ABNORMALITIES
• 23 pairs of chromosomes
• 50+ different chromosomal abnormalities
– Too many chromosomes
– Too few chromosomes
• Vast majority of chromosomal abnormalities
are lethal (spontaneous abortion)
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HUMAN KARYOTYPE
Most human cells
contain 46 chromosomes:
• 22 pairs of chromosomes
named autosomes
• 2 sex chromosomes (X,Y):
XY – in males
XX – in females
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GENOTYPES vs PHENOTYPES
• In autosomes chromosomes exists in homologous pairs
• At each locus (except for sex chromosomes) there are 2
gene alleles. One allele at an individual locus on each of
the pair of chromosomes. This constitutes the
individual’s genotype at that locus and for that individual
gene.
• The expression of a genotype is termed a phenotype.
For example, hair color, weight, or the presence or
absence of a disease
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HAPLOID AND DIPLOID CELLS
Remember that body (somatic) cells have
chromosomes arranged in pairs (diploid), whilst
gametes (sperm and ova) have only one member of
each pair (haploid)
Diploid cells will therefore have gene alleles
arranged in pairs*, whilst the gametes will have
only a single gene allele
*except in males where the Y chromosome is shorter than the X
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DOMINANT AND RECESSIVE
ALLELES
For example in human eye
colour – brown eyes (B) is
dominant to blue (b).
SPERM
B
EGGS
Many genes exist in two
allelic forms in which one
allele is dominant to the
other which is termed
recessive
b
B BB Bb
b
Bb bb
BB - Brown eyes
Bb - Brown eyes
bb - Blue eyes
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DOMINANT AND RECESSIVE
ALLELES
SPERM
B
EGGS
In diploid somatic cells the
genotype with respect to an
individual gene (e.g. the gene
for eye colour) can be described
as homozygous if both alleles
for the gene are the same – so
could be homozygous dominant
(BB) brown or homozygous
recessive (bb) blue.
b
B BB Bb
b
Bb bb
BB - Brown eyes
Bb - Brown eyes
bb - Blue eyes
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DOMINANT AND RECESSIVE
ALLELES
Note: the convention is that:
• DOMINANT allele (CAPITAL letter)
• recessive allele (lower letter)
B
EGGS
If the alleles are different (Bb) the
condition is called heterozygous and
in this example the individual would
be brown eyed because brown (B) is
dominant to blue (b).
SPERM
b
B BB Bb
b
Bb bb
BB - Brown eyes
Bb - Brown eyes
bb - Blue eyes
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TRY THIS EXAMPLE
Two brown eyed parents have three children – two
brown eyed and the other blue.
Q. What must the genotypes of the parents be?
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THE ‘PUNNETT’ DIAGRAM
A ‘Punnett’ diagram is used to
work out the various
combinations of gene alleles
B
EGGS
E.G. If both parents are
homozygous brown eyed the
possible combinations are:
SPERM
b
B BB BB
b
BB BB
All children will be
brown eyed
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THE ‘PUNNETT’ DIAGRAM
EGGS
Another possible combination
might be:
SPERM
• if one parent is homozygous
B b
(BB) and the other
B BB Bb
heterozygous (Bb)
• the heterozygous children
b BB Bb
are carriers but do not
display the phenotype of All children still brown eyed
but 50% chance homozygous
blue eyes themselves
and heterozygous
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THE ‘PUNNETT’ DIAGRAM
The final possibility is if
both parents are
heterozygous (Bb)
B
EGGS
..this results in the
possibility of having both
blue eyed as well as brown
eyed children….
SPERM
b
B BB Bb
b
BB bb
25% chance of a
blue eyed child
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MEDICAL GENETICS
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MEDICAL GENETICS
When studying genetic disorders, 6 general
patterns of inheritance are observed:
–
–
–
–
–
–
Autosomal recessive
Autosomal dominant
Autosomal Co-dominant
X-linked recessive
X-linked dominant
Mitochondrial
17SLT
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MEDICAL GENETICS
Autosomal Recessive
•
•
•
Recessive inheritance
means both genes in a
pair must be defective to
exhibit the defect
The disease appears in
male and female children
of unaffected parents
e.g. cystic fibrosis
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MEDICAL GENETICS
Autosomal dominant
• The disorder appears
when only one of the two
genes of a chromosome
pair is defective
• Affected males and
females appear in each
generation of the
pedigree
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MEDICAL GENETICS
Autosomal dominant
• Mothers or fathers can
transmit the phenotype to
both sons and daughters
• The risk of a mutation
carrier transferring disease
to offspring amounts to
50%.
• e.g. Huntington’s disease
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MEDICAL GENETICS
FOXP2 gene
FOXP2 is a protein that in humans is encoded by the
FOXP2 gene, which is located on human
chromosome 7. In humans, mutations of FOXP2
cause a severe speech and language disorder. The
gene is transmitted in an autosomal dominant
pattern. The following article provides some
background to the gene and its expression in
humans.
Read more about FOXP-2 and link to SLI in Cummings, L p284
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CO-DOMINANT OR MULTIPLE
ALLELE INHERITANCE
The gene has three allelic
forms A and B are codominant and O is recessive
Genotype
Phenotype
AA
A
AO
A
BB
B
BO
B
AB
AB
OO
O
(ABO BLOOD GROUPS)
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GENES PRESENT ON THE
SEX CHROMOSOMES
The X chromosome is larger than the Y chromosome and
has a segment for which there is no equivalent on the Y
chromosome. This segment contains genes where the
alleles are not matched by alleles on the Y chromosome.
In males the single allele on the X chromosome will
always show itself in the character (phenotype) of the
individual. In females with two X chromosomes a
recessive allele may be masked by a dominant allele on
the other X chromosome.
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GENES PRESENT ON THE
SEX CHROMOSOMES
Boys gain their X chromosome
from their mother – never their
father. Girls gain one X
chromosome from each
parent.
SPERM
EGGS
X
Y
X
XX XY
X
XX XY
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GENES PRESENT ON THE
SEX CHROMOSOMES
* mutated genes are not always recessive or
damaging
SPERM
XN
EGGS
When considering sex linked traits
we must take account of the
chromosome type (X or Y) as well as
the allele present (or not present) on
each.
For example consider a gene on the
X chromosome, which has a
‘Normal’ dominant form (N) and a
mutant* recessive form (n)
XN
Xn
Y0
♀NN ♂ N♀Nn
♂ n-
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GENES PRESENT ON THE
SEX CHROMOSOMES
X linked recessive traits
•
•
Many more males than females
show the condition
All the daughters of an affected
male will carry the condition and
are ‘carriers’.
None of the sons of an affected
male show the condition or are
carriers.
(Remind yourself why this must be so)
E.g. haemophilia
SPERM
XN
EGGS
•
XN
Xn
Y0
♀NN ♂ N♀Nn
♂ n-
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GENES PRESENT ON THE
SEX CHROMOSOMES
X linked recessive traits
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GENES PRESENT ON THE
SEX CHROMOSOMES
X linked recessive traits
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GENES PRESENT ON THE
SEX CHROMOSOMES
X-linked DOMINANT trait
Affected males pass the disorder to all daughters but
to none of their sons
Affected heterozygous females and unaffected males
pass the condition to half their sons and daughters
e.g. fragile X syndrome
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GENES PRESENT ON THE
SEX CHROMOSOMES
X-linked DOMINANT trait - e.g. fragile X syndrome
Fragile X syndrome, or Martin-Bell syndrome, is a
genetic syndrome which results in a spectrum of
characteristic physical, intellectual, emotional and
behavioral features which range from severe to mild in
manifestation. The syndrome results in a failure to
express a protein which is required for normal neural
development.
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GENES PRESENT ON THE
SEX CHROMOSOMES
X linked dominant traits
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MEDICAL GENETICS
Mitochondrial inheritance
In sexually reproducing
organisms, mitochondria are
normally inherited exclusively
from the mother. The
mitochondria in mammalian
sperm are usually destroyed by
the egg cell after fertilization.
e.g. Leber's hereditary optic
neuropathy (LHON)
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MEDICAL GENETICS
Mitochondrial inheritance
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
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MEDICAL GENETICS
Mitochondrial inheritance
Leber’s hereditary optic
neuropathy (LHON) or Leber
optic atrophy is a
mitochondrially inherited
(mother to all offspring)
degeneration of retinal
ganglion cells (RGCs) and
their axons that leads to an
acute or sub acute loss of
central vision.
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CHECK YOUR UNDERSTANDING
What is the meaning of (i.e. in relation to genetic concepts):
•
•
•
•
•
•
•
Chromosomes
Autosomes
Alleles (homozygous and heterozygous
X-linked
Y-linked
Dominant
Recessive
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