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In general, genes act as the instruction for building proteins, such as structural proteins, enzymes, signalling
proteins (e.g. hormones) and regulatory proteins, in the body (see Figure 2 below).
http://www.ncbi.nlm.nih.gov/nuccore/NC_000011.9?report=fasta&from=5246696&to=5248301&strand=true
Alleles
Alleles are alternative forms of a gene, that is code for alternative forms of trait (e.g. Hair colour B for brown
hair and b for blonde hair). Alleles are located at a specific position (locus, plural: loci) on the chromosome
(chromosome is the structural organisation of DNA). Because cells (except gametes) contain paired
chromosomes, virtually every cell in the body has a pair of each gene (and therefore, two alleles).
For example, ABO blood group of an individual is determined by alleles of the ABO gene. There are three
main alleles of this gene A, B and O which are located at a specific position on the chromosome 9. Because
chromosomes (and so genes or alleles) are paired, each individual has two ABO alleles which interact to dictate
his/her blood type. For instance, a person with the B allele and O allele will have the B blood type (because O
allele is recessive and B allele is dominant), whereas a person with the A allele and B allele will have the AB
blood type (this interaction, in which both dominant alleles are expressed, is known as co-dominant ).
It is important to note that gametes (sperm and eggs) contain single copies of every allele in the human genome.
That is, chromosomes in gametes are not paired, so gametes contain 23 different chromosomes (22 autosomes
and one sex chromosome). At fertilisation, the sperm and ovum fuse to form an embryo which contains two
copies of each autosomes and two sex chromosomes, that is 46 chromosomes in total). Therefore, one allele is
received from each parent when gametes fuse.
Dominant
An allele that masks or suppresses the expression of a recessive allele. Its presence always leads to
expression of a dominant allele (i.e., dominant allele is expressed in F/F or F/t).
ii.
Recessive
An allele that is expressed only in the homozygous recessive genotype (i.e., two identical copies of
recessive allele e.g. f/f or b/b).
Genetic disorders can be caused by either dominant (e.g. Huntingtons disease) or recessive (e.g. albinism and
cystic fibrosis) alleles.
Because the presence of a dominant allele always results in the expression of its trait, dominant genetic
disorders have a higher chance to get passed to the next generation, than that of recessive genetic disorders.
Recessive genetic disorders that absent when dominant alleles are either homozygous or heterozygous. Unlike
dominant genetic disorders, a single recessive allele (responsible for the disorder) cannot cause the genetic
disorder (e.g. A/a where A is the normal allele and a is the albinism allele). Individuals with such recessive
heterozygous genotype are said to be a carrier of the recessive genetic disorder. Carriers will pass these
harmful genes (i.e., recessive allele responsible for the disorder) onto offspring.
Punnetts square
The Punnetts square is a simple way to represent the pairing of all possible gamete types for a single trait. It is
used to predict genotypes of offspring and expected frequency (or probability) from known genotypes of two
parents.
The genotypic ratio is the ratio of the resultant genotypes. In the table above, the genotypic ratio is X/X:X/Y =
1:1, which means there is a 50% chance of receiving either X/X or X/Y.
The phenotypic ratio is the ratio of the phenotypes expressed by the resultant genotypes (X/X is female and
X/Y is male). The phenotypic ratio of the example above is therefore female:male = 1:1.
It is important to note that the probability of genotype (i.e., the genotypic ratio) never changed, that is, each
offspring has the same probability of receiving genotype. And each is an independent event which has no
influence on the next one (e.g. older siblings genotype has no influence on the probability of genotype that
younger siblings will have).
Pedigree
A pedigree is one of major avenues for identifying carriers of detrimental genes; used in diagnosis of genetic
disorders, and genetic screening and counselling. It represents the family history by tracing a genetic trait
through several generations, which helps predict the future.
Carrier
* Apply the rules of traits inheritance modes to deduce the genotypes of any family member with unknown genotype.
Modes of Inheritance
(a) Autosomal dominant-recessive inheritance
The mode of inheritance in which the gene responsible for the traits of interest is carried on one of the
autosomes (non-sex chromosomes). One allele is dominant over the other in appearance. Examples of this
inheritance are widows peaks, dimples and freckles. The trait of interest can be either dominant or recessive.
i.
Autosomal dominant
This mode of inheritance has a vertical pedigree pattern (see Figure 3); that is, the trait is expressed (or
found) in multiple generation.
ii.
Autosomal recessive
The autosomal recessive inheritance has a horizontal pedigree pattern (see Figure 4); that is, the trait
(or disorder) is found in the same generation but often skips the generations.
normal
colour blindness (recessive allele)
Note that Y chromosome does not carry
colour-blindness allele
Based on this Punnett square information, determine the proportion of children will be colour blind.
Also, compare the phenotypic ratio of male offspring and of female offspring, and if there is a difference,
explain why.
Answer:
There is a 25% chance of being affected.
All female offspring will have normal vision, but there is a 50% chance of becoming a carrier of colourblindness. For male offspring, there is a 50% chance of being affected (X cb/Y).
Red/green colour blindness is therefore more common in males. This is because they have one Y chromosome
which does not carry either normal allele (CB) or colour-blindness allele. Thus, males with one affected Xlinked allele (X cb/Y) will become affected (which is typically inherited from his mother).
Now, lets look at the pedigree pattern of this mode of inheritance (see Figure 6).
Knights move:
may appear to
skip a generation
Usually affected
grandfather to
grandson
It is important to note that transmission of X-linked recessive genetic disorder never occurs between male and
male (i.e., father to son). This is because father always pass his Y chromosome to his son, and son always
receives X chromosome from his mother (who may be a carrier female).
Genotype
I or I Ao
I BB or I Bo
I oo
I AB
AA
Genetic Disorders
In addition to the genetic disorders introduced in the previous chapters (which involve alleles or a single gene),
there are other types of genetic disorders such as chromosomal disorders and multifactorial (polygenic)
disorders. Characteristics of these types of genetic disorders are summarised in the box below:
Autosomal trisomy
Autosomal trisomy is a trisomy in which there are three copies of a particular autosome (non-sex
chromosome), instead of the normal two (a pair). For example, Downs syndrome is a trisomy-21
which means there are three copies of chromosome 21 (see Figure 7 below).
ii.
Figure 8: Karyotype of Turner syndrome (on the left) and of Klinerfelter syndrome (on the right).
Another example is Klinefelter syndrome (47, XXY) is caused by one excess X chromosome in foetal
cells, producing a male foetus with 47 chromosomes. This syndrome is associated with pubertal failure,
infertile, slightly lower IQ than his siblings (but still within the normal range), often tall with female
distribution of body fat (i.e., larger hips and breasts than normal 46, XY males).
This is a way of reporting karyotypes. Normal karyotype is represented as 46, XX or 46, XY (the number is referring to the total number of all
chromosomes present).
3
Over 95% of cases is reported to be resulted in early spontaneous loss of the foetus
10
Possible mood disturbances may include: explosiveness, apathy, aggression, alcohol abuse etc.
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The concept described in the first paragraph can be represented in a continuum of diseases (see Figure 9 below).
More examples of multifactorial and polygenic disorders are provided in the table below.
You may wonder: Okay, I get that multifactorial diseases involve both genetic and environmental factors. But
what if a multifactorial disease involves more than one gene? Wouldnt it be then polygenic by definition?
In some other genetic textbooks or journal articles, the term multifactorial inheritance implies that a disease is
caused by the interaction of several adverse genetic and environmental factors5.
In general, multifactorial diseases involve the interaction between genetic and environmental factors, whereas
polygenic disorders involve multiple genes. Moreover, environmental factors (in general) have no effects on
polygenic disorders; that is, congenital (born with disorders).
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Complex Diseases
There are only some disorders that are caused by mutations in a single gene (e.g. sickle cell disease and cystic
fibrosis). The causes of many other disorders, however, are much more complex and may be inherited as
complex traits.
Common diseases and disorders, such as heart disease, diabetes and obesity, do not have a single genetic cause.
However, they are associated with the effects of multiples gene in combination with lifestyle and environmental
factors. Genetic researchers are learning more about genetics of common disorders, and studying the role of
various genes that play in disease. Their study and work are not limited to genetic disorders, but also include
common illnesses such asthma, arthritis and Alzheimer disease.
In general, genetic factors affect the susceptibility to these complex diseases. It is important to note that genetic
factors interact with environmental factors, which means that, if lifestyle and environmental factors are wellcontrolled (e.g. regular exercise and healthy diet), the risk of obesity will be reduced. Therefore, even if,
individuals have received obesity genes from their parents, there is still a good chance of preventing it.
Figure 10: a model of obesity (Note: there are other models of obesity).