genetic course

lecture (4)
Lethal alleles and multiple alleles
Dr. israa hussein hamzah
email: esraa_hassan17@yahoo.com
szsh@uomustansiriyah.edu.iq
Reference book: genetic (Conceptual-
Approach) fourth edition (2012)
Author: Benjamin C. Pierce
Lethal genes are mutant genes and result in the death of the individual which
carries them. Death of the individual occurs either in the prenatal or postnatal
period prior to sexual maturity. A fully (completely) dominant lethal allele kills
both in homozygous and heterozygous states. Individuals with a dominant lethal
allele die before they can leave progeny. Therefore, the mutant dominant lethal is
removed from the population in the same generation in which it arose. Recessive
lethal genes kill only when they are in a homozygous state and they may be of two
kinds : 1. one which has no obvious phenotypic effect in heterozygotes and 2. one
which exhibits a distinctive phenotype when heterozygous.
The completely lethal genes usually cause death of the zygote, later in the
embryonic development or even after birth or hatching. Complete lethality, thus, is
the case where no individuals of a certain genotype attain the age of reproduction.
However in many cases lethal genes become operative at the time the individuals
become sexually mature. Such lethal genes which handicap but do not destroy
their possessor are called subvital, sublethal or semilethal genes. The lethal alleles
modify the 3:1 phenotypic ratio into 2 : 1.
Examples of Lethal Alleles

A. Lethal alleles in plants. In plants, recessive

lethal alleles are known which produce albinism, where absence of chlorophyll is lethal
(fatal) to them. Following two examples illustrate this fact :
1. In snapdragons (Antirrhinum majus) three types of plants occur :
1. green plants with chlorophyll
2. yellowish green plants with carotenoids, usually are referred as pale green, golden
or auria plants and
3. white plants without any chlorophyll.
The homozygous green plants have the genotype CC and the homozygous white plant
has the genotype cc. The auria plants have the genotype Cc because they are
heterozygotes of green and white plants. When two such auria plants are crossed, the
F1 progeny has identical phenotypic and genotypic ratio F1 : 2 : 1 (viz., 1 green (CC) : 2
auria (Cc) : 1white (cc). But the white plants because lack chlorophyll pigment,
therefore, die to modify the ratio of 1 : 2 : 1 into1 : 2 or 2 : 1. In this case the
homozygous recessive genotype (cc) is lethal.
F1 heterozygote : : Auria X Auria
Cc Cc

F2 : 1 CC : 2 Cc : 1cc
Green Auria White (lethal}
.
Thus, c allele exhibits a lethal effect when homozygous and a distinctive phenotypic
effect (e.g., auria) when heterozygous.
2. In maize (Zea mays) the amount of chlorophyll is controlled by a recessive allele
(g) which exhibits a lethal effect in homozygous (gg) and in heterozygous condition
(Gg) has phenotype similar to homozygous condition for dominant gene GG. It
modifies 3 : 1 phenotypic ratio into 2 : 1.
F1 heterozygote : Green X Green
Gg Gg
 
F2 : 1 GG : 2 Gg : 1 gg
Green Green White (lethal) or 1 GG : 2 Gg
B. Lethal alleles in animals. Among animals, the following three
examples exhibit the role of recessive lethal alleles :
:1. The inheritance of mouse body colour was studied by the French geneticist, L.
Cuenot in 1905. The coat colour of mice is governed by a multiple allelic series in
which
A allele determines agouti or mousy-coloured coat

AY allele determines yellow coat and a allele forms black coat.

The dominance hierarchy is as follows : A Y >A>a. The AY allele also acts as a
recessive lethal, since in the homozygous state (A YAY), it kills the individual in early
embryonic stage (i.e., during gastrulation). Thus, when two yellow coated
heterozygotes (AYA) are crossed, they produce a progeny showing a ratio of 2:1
since homozygous yellow (AYAY) individuals are never borned due to lethal effect of
AY gene
Parents : Yellow X Yellow
AYA A Ya
(Hybrid of yellow and agouti) ↓ (Hybrid of yellow and black)
Progeny : 1AYAY : 2 A YA : 1 Aa
Homozygous Yellow Heterozygous Agouti
(die in uterus) Yellow
or 2 Yellow : 1 Agouti or 2:1.
 
 
 
 
 
 
 
 
One gene may contribute to several visible characteristics
Mendel derived his laws from studies in which one gene determined one trait .
The phenomenon of a single gene determining a number of distinct and seemingly
unrelated characteristics is known as pleiotropy. Since genetics now know that each
gene determines a specific protein and that each protein can have a cascade of effects
on an organism, we can understand how can pleiotropy arises .
Some alleles may cause lethality
A significant variation of pleiotropy occur in alleles that not only produce a visible
phenotype but also affect viability . Mendel assumed that all genotypes are equally
viable such as representative of each genotype have an equal rate of survival. If this
were not true, and a large percentage of, say, homozygous for particulare allele died
before germination or birth, you would not be able to count theme after birth, and this
alter the 1:2:1 genotype ratio and the phenotypic ratios predicted for the F2 generation.

 
.
Among the aboriginal Maori people of new Zealand, for
example ,many of the men develop frequent respiratory problems
and are also sterile. Researchers have found that the fault lies with
the recessive alleles of a single gene. the gene normal dominant
allele specifies a proteins necessary for the action of cilia and
flagella, both of which are hairlike structure extending from surfaces
of some cells. In men who are homozygous for the recessive alleles,
however ,cilia that normally clear the airways fail to work effectively
and flagella that normally propel sperm fail to do their job. Thus one
gene determines a protein that indirectly affects both respiratory
function and reproduction
Most of the genetic systems that we have examined so far consist of two
alleles. In Mendel’s peas, for instance, one allele encoded round seeds and
another encoded wrinkled seeds; in cats, one allele produced a black coat and
another produced a gray coat. For some loci, more than two alleles are
present within a group of organisms—the locus has multiple alleles.
(Multiple alleles may also be referred to as an allelic series.) Although there
may be more than two alleles present within a group of organisms, the
genotype of each individual diploid organism still consists of only two alleles.
The inheritance of characteristics encoded by multiple alleles is no different
from the inheritance of characteristics encoded by two alleles, except that a
greater variety of genotypes and phenotypes are possible.
The ABO blood group Another multiple-allele system is at the locus for the
ABO blood group. This locus determines your ABO blood type and, like the
MN locus, encodes antigens on red blood cells. The three common alleles
for the ABO blood group locus are: IA, which encodes the A antigen; IB,
which encodes the B antigen; and i, which encodes no antigen (O). We can
represent the dominance relations among the ABO alleles as follows: IA > i,
IB > i, IA = IB. Both the IA and the IB alleles are dominant over i and are
codominant with each other; the AB phenotype is due to the presence of an
IA allele and an IB allele, which results in the production of A and B
antigens on red blood cells. A person with genotype ii produces neither
antigen and has blood type O. The six common genotypes at this locus and
their phenotypes are shown in figure . Antibodies are produced against any
foreign antigens. For instance, a person having blood-type A produces anti-
B antibodies, because the B antigen is foreign. A person having blood-type B
produces anti-A antibodies, and someone having blood-type AB produces
neither anti- A nor anti-B antibodies, because neither A nor B antigen is
foreign. A person having blood-type O possesses no A or B antigens;
consequently, that person produces both anti-A
Polygenic inheritance
Human features like height, eye color, and hair color come in
lots of slightly different forms because they are controlled by
many genes, each of which contributes some amount to the
overall phenotype. For example, there are two major eye color
genes, but at least 14 other genes that play roles in determining
a person’s exact eye color

Looking at a real example of a human polygenic trait would get

complicated, largely because we’d have to keep track of tens, or
even hundreds, of different allele pairs (like the 400 involved in
height!).
Key terms
Term Meaning
Multiple alleles: A gene that is controlled by more than two
alleles
Pleiotropy: When one gene affects multiple characteristics
Lethal allele: Allele that results in the death of an individual
Polygenic trait: Traits that are controlled by multiple genes
 Table :for trait determined one gene extensions to Mendel's
Analysis explain alterations of the 3:1 Monohybrid ratio.
 

What Mendel described Extension Extensions effect on Extensions effect on ratios

heterozygous resulting from an F1XF2 cross
phenotype
Complete dominance Incomplete Unlike either Phenotype coincide with
dominance ,codo homozygous genotype in ratio of 1:2:1
minance
Two alleles Multiple alleles Multiplicity of A Series of 3:1 ratios
phenotypes
Are alleles are equally viable Recessive lethal No effect 2:1 instead of 3:1
alleles
One gene determines one trait Pleiotropy: one Several traits affected Defferant ratios depending on
gene influences in different dominance relations for each
several traits ways ,depending on effected trait.
dominance relations
GENETIC INTERACTION
The gene is a chemical determiner. Whereas a phenotypic trait results
from the combined action of many genes and their products constantly
interacting with the environment. The environment includes not only
ecological factors such as temperature and the amount or quality of light,
but also internal factors such as hormones and enzymes. The enzymes are
proteins and the specific molecular organization of protein is determined
by genes. The enzymatic proteins perform catalytic function in various
cellular chemical (metabolic) reactions and causing the splitting or union
of various molecules.
Each cellular chemical reaction involves stepwise conversion of one
substance called precursor into another, called end product. Each step
being mediated by a specific enzyme. All the subsequent steps of a
chemical reaction constitute the biosynthetic pathway. Thus, a simplest
biosynthetic pathway includes various steps, each step is catalyzed by a
specific enzymatic protein and each enzymatic protein in its turn depends
on a specific gene for its production. For example, we may consider a
simple biosynthetic pathway which transforms a precursor substance ‘P’
into the end product ‘C’ in following three subsequent steps :
P (precursor) e1 A — e2 B e3 C end product
In this biosynthetic pathway each metabolite (A, B, C) is produced by the catalytic
action of
different enzymes (e1, e2,e3.....ex, specified by different wild type genes
(g+1,g+2,g+3,
}. When more than two or more genes become involved in the specification of
enzymes for different steps of a common biosynthetic pathway, the phenomenon
of genetic interaction occurs. If substance C is essential for the production of a
normal phenotype and the recessive mutant alleles g1, g2, g3 produce defective
enzymes, then a mutant or abnormal phenotype would result from a genotype
homozygous recessive at any of the three loci. If wild gene g3 + becomes mutant,
the conversion of metabolite B to C does not occur and substance B tends to
accumulate in excessive quantity; if g2+ becomes mutant, substance A will
accumulate. Thus, the mutant genes caused “metabolic blocks” in synthetic
pathway.
An organism with a mutation only in gene g2+ could produce a normal
phenotype, if it was given either substance B or C, but an organism with a
mutation in gene g3+ has a specific requirement for substance C for the
production of normal phenotype. Thus, gene g3+ becomes dependent
upon g2+ for its expression as a normal phenotype. If the genotype is
homozygous for the recessive g2 allele, then the biosynthetic pathway
ends with substance A. Neither g3+ nor its recessive allele g3 has any effect
on the phenotype. Thus, genotype (g2g2) can hide or mask the phenotypic
expression of alleles at the g3+ locus. Originally a gene or locus which
suppressed or masked the action of a gene at another locus was
termed epistatic gene.
The gene or locus which was suppressed by a epistatic gene was
called hypostatic gene.
Later studies revealed the fact that both loci or genes (i.e., epistatic and
hypostatic) could be epistatic to one another. Presently, the term epistasis
(Greek, standing upon) is used for almost any type of allelic genetic
interaction
Difference Between Dominance and Epistasis
The phenomenon of dominance involves intra-allelic gene suppression, or
the masking effect which one allele has upon the expression of another
allele at the same locus, while the phenomenon of epistasis involves inter-
allelic gene suppression or the masking effect which one gene locus has
upon the expression of another. The classical phenotypic ratio of 9 : 3 : 3 : 1
observed in the progeny of dihybrid parents becomes modified by epistasis
into ratios which are various combinations of the9 : 3 : 3 : 1 groupings.