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BASIC GENETIC CONCEPTS
M.Tevfik Dorak, MD, PhD
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Dominant vs Recessive
Mendelian inheritance patterns usually
apply to traits governed by a single gene. Most characters, however, are
determined by multiple genes or by an interaction of genes and the environment.
The inheritance of quantitative characteristics that depend on several genes is
called polygenic inheritance. A combination of genetic and environmental
influences is known as multifactorial inheritance. Diseases with
multifactorial inheritance are called complex genetic diseases.
A gene may act as dominant
or recessive, although dominance or recessiveness concerns the
phenotype. But these are not the only modes of action (incomplete dominance and
co-dominance are possible). Examples of dominant characters include dark hair
(to blonde hair); brown eyes to blue eyes (as originally thought by Davenport
& Davenport in their 1907 Science paper 'available through JSTOR, but also see more recent views here); and
lobed ears to unlobed ears. Possible examples of recessive characters are,
therefore, blonde hair and blue eyes. Ability to taste a chemical (PTC) is
dominant to inability to taste it. The grey body colour of Drosophila is
dominant to black. Yellow is dominant to green in seed cotyledons of Pisum
sativum used in Mendel's experiments. A dominant allele usually codes for a
functional product and continues to do so in heterozygous form (however, beware
of dominant negative and haploinsufficiency; see glossary and Clinical Genetics). A
recessive allele usually directs the synthesis of a non-functional product
causing the lack of the product in homozygous form. For example, a green seed
is always homozygous but a yellow one may be heterozygous (yellow is dominant
to green).
Recessive sex-linked genes do not
require homozygosity for expression (coat color in cats, various sex-linked
diseases such as hemophilia and red-green color-blindness in humans). A rare
X-linked dominant trait is the blood type Xga (males
expressing this trait would transmit it to all daughters but not to a son).
Incomplete dominance (also called
blending, semi-dominance): The four-o'clock plant (the snapdragon, Antirrhinum),
for example, may have flowers that are red, white, or pink. Plants with red
flowers have two copies of the allele R for red flower color (pure line
for red) and hence are homozygous RR. Plants with white flowers have two
copies of the allele r for white flower color (pure line for white) and
are homozygous rr. Plants with one copy of each allele, heterozygous Rr,
are pink—a blend of the colors produced by the two alleles. Fur color of
Andalusian Fowl is another example: black and white are partial-dominant,
therefore heterozygotes are grey.
Co-dominance: ABO
blood groups (A and B are co-dominant; O is recessive) and HLA transplantation
antigens (HLA-A,B,C,DR,DQ,DP) are co-dominantly expressed. The gene responsible
for sickle cell anemia has two co-dominant alleles: HbA (normal gene) and HbS
(sickle cell gene). HbAA is normal, HbSS is diseased and HbAS is mildly anemic
and protective for malaria (hence its selection). White or Dutch clover (Trifolium
repens) leaf patterns are co-dominantly expressed. A heterozygous plant
shows both patterns superimposed, while homozygotes for the other two patterns
show a single pattern.
Sex-influenced dominance: A
dominant expression that depends on the sex of the individual. An example is
the horns in sheep (dominant in males, recessive in females). Another one is
the plumage in domestic fowl: autosomal alleles whose expression is modified by
sex hormones; the same genotype (hh) results in long, more curved and
pointed plumage in cocks; shorter and more rounded in hens. Certain coat
patterns in cattle, baldness patterns, breast development and facial hair (as
well as all secondary sex characters) in humans are also sex-influenced traits.
An autosomal dominant trait that controls precocious puberty is expressed in
heterozygous males but not in heterozygous females. Affected males undergo
puberty at 4 years of age or earlier. Heterozygous females are unaffected but
pass this trait on to half of their sons (confusing the pattern with a
sex-linked trait).
A different phenomenon is temperature-influenced
expression (in Himalayan rabbit and Siamese cat fur color). The
temperature-sensitive allele causes say, darker patches in extremities, ears
and nose.
Further points: As in
rabbit fur and mouse coat color determination, dominance relationships between
alleles may be more complicated. The reasons for dominance may be related to
the activity of an enzyme coded by the relevant gene. Mendel's yellow pea
allele is dominant because the gene involved codes for the breakdown of
chlorophyll (which is green). In the homozygous recessive case, no functional
enzyme will be present, chlorophyll breakdown cannot occur and the seeds remain
green. In a situation called epistasis, one gene affects the expression
of another gene that is not linked (multigenic determination of a phenotype).
The masked gene is said to be hypostatic to the epistatic gene.
An epistatic-hypostatic relationship between two loci is similar to a
dominant-recessive relationship between alleles at a particular locus.
Genomic imprinting, methylation
and penetrance are other factors that may influence the expression of
characters. If one of the possible genotypes is an embryonic lethal, the
observed proportions would be different from expected ones (also remember the cytoplasmic
male sterility in plants).
Having a disease-causing gene does
not always mean having the disease. In phenylketonuria
(PKU), avoiding phenylalanine-containing food prevents ill effects of the
mutant gene; and in xeroderma
pigmentosum, avoiding ultraviolet radiation prevents the development of
melanoma. On the other hand, having a protective gene may prevent the ill
effects of an environmental agent. The gene for the xenobiotic enzyme CYP1A1 on
chromosome 15 may activate the polycyclic aromatic hydrocarbons (PAH) depending
on the allele. PAHs are present in cigarette smoke and those who have the
non-activating allele may not be affected from the carcinogenic effects of PAH.
SuperLectures on Genetics by RM Fineman: Part I and Part II
Encyclopedia of Genetics Encyclopedia of Life Sciences Encyclopedia of Medical Genomics & Proteomics
M.Tevfik Dorak, MD, PhD
Last
updated on 28 November 2005
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