© 2002, G. Holzer, all rights reserved.

Mendelian Genetics

Content : - Experiments with peas - Punnett square - Test Cross - Independent Assortment - Blood groups - Sex linkages - Genetic Maps - Incomplete dominance - Epistasis - Genetic Diseases - Autosomal recessive - Autosomal dominant - Sex linked - extra chromosome

- Comments and Questions - Back to Course Syllabus

Mendel’s garden peas
Mendel     flower     pea     variations    
The historical aspects of Mendel's discoveries are outlined in the texbook. Different forms of a gene (one on the maternal chromosome, one on the paternal chromosome) are called alleles . If two alleles are identical, they are said to be homozygous. If they are different they are called heterozygous . The two heterogeneous gene for the same trait may not be expressed equally. In case one allele is expressed, but not the other one, the expressed allele is called dominant . The allele which is not expressed is said to be recessive . In order for a recessive trait to be expressed, the two alleles have to be homozygous i.e. the recessive gene has to be present on the maternal as well as on the paternal chromosome. In contrast a dominant trait is expressed as long as one dominant allele is present i.e. one of the two alleles can be recessive. Of course the dominant trait is also expressed if both alleles are dominant homozygous.

The garden pea can propagate through self pollination or through pollination by a different plant. Mendel had several true breeding varieties, i.e. a certain plant lines which produce white flowers from one generation to the next, or produce peas with shriveled seeds from one generation to thenext. In his first experiments Mendel was cross-breeding two true breeding varieties. He cut the anthers of a purple flower to prevent self pollination and used the pollen of a white flower to pollinate the purple flowered plant. After planting the seeds of the plant Mendel observed the color of the flower. He found that all offspring in the first generation was purple. When the first generation was allowed to self pollinate, the second generation had a ratio of 3:1 ( purple flower : white flower). The following diagram illustrates the processes on the gene level

Since the peas are white flowered only if the two alleles for the white flower are present, it must be a recessive allele. A heterozygous plant ( allele for the purple and the allele for the white flower are present) has a purple flower, identifying purple as the dominant trait. To distinguish between genes and traits, the term genotype is used to specify which genes are present in an individual ( allele for purple vs allele of white flower) and the term phenotype is used when referring to the visible trait of an individual (does the plant have a purple or white flower). In the above example the phenotype ratio is 3:1 (purple : white), whereas the genotype is 1:2:1 ( homozygous purple, heterozygous purple/white, homozygous white)

In an alternative way to the above diagram, Mendel’s experiment can be illustrated by a Punnett square
From these experiments Mendel derived the principle of segregation We can formulate this principle using the terms of modern genetics. Organisms with a diploid number of chromosomes inherit two genes for each trait (one on the paternal chromosome and one on the maternal chromosome). The genes segregate from each other during meiosis. Each gamete has the same chance of obtaining either one of the two genes.

Test cross

In a test cross the first generation hybrid of a plant line is crossed with a true breeding plant which is homozygous for the recessive trait. In case of the above example, a purpled flower hybrid of the first generation is crossed with a true breeding white flowered plant. If the offspring is purple then the hybrid must have been homozygous dominant, if the offspring is purple : white flowered at a 1:1 ratio, the hybrid must have been heterozygous.

Independent Assortment
Different alleles segregate independently of each other, provided they are located on different non-homologous chromosomes ( locus of traits ) This is known as Mendel's second law of heredity and is illustrated by the following experiment with garden peas:

Pod color : green (Y) = dominant; Pod Shape: Inflated (C) = dominant
Pod color: yellow (y) = recessive; Pod shape: constricted (c) = recessive

First, the two pure, homozygous breeding lines are crossed
1. green, inflated breeding line : which has two identical, dominant alleles for green pod color (YY) and two identical, dominant alleles for inflated pod shape (CC)

2. yellow, constricted breeding line : which has two identical recessive alleles for yellow pod color (yy) and two identical recessive alleles for constricted pod shape (cc)

During meiosis the dominant alleles can segregate into two possible gametes, which are identical:
YYCC forms gametes YC and YC

The recessive alleles will also segregate into two identical gametes:
yycc forms gametes yc and yc

The gametes can combine as shown in the Punnett square below.

Possible maternal
gametes		 Pod Color
Pod Shape
YC YC
Possible
paternal
gametes		 yc Y y C c Y y C c All green
Inflated
yc Y y C c Y y C c

The F1 generation consists of identical individuals: Y y C c

Self fertilization of the F1 generation
The gene pairs Yy and Cc will segregate during meiosis into gametes with the following four possible gene combinations:

Yc, yc ,yC, YC

If you have forgotten the mechanism of random alignment of paternal and maternal chromosomes and meiosis I and meiosis II, follow the chart below.

The four paternal and four materal gametes combine during fertilization to form zygotes which have 4 x 4 = 16 possible gene combinations. This is shown in the Punnett square below.

Possible maternal gametes Pod Color
Pod Shape
YC Y c yc y C
Possible
paternal
gametes		 YC YYCC YYC c Y y C c Y y CC 9/16 green
Inflated
Y c YY C c YY cc Y ycc Y y C c 3/16 green
Constricted
yc Y y C c Y ycc yycc yy C c 3/16 yellow
Inflated
y C Y y CC Y y C c y y C c yy C c 1/16 yellow
constricted

In his experiment Mendel observed this phenotypic ratio of 9:3:3:1, confirming that gene pairs which are located on different, non-homologous chromosomes segregate into gametes indepently of each other.

Blood Type Groups

The surface of red blood cells contains sugar molecules, which are linked to membrane lipids or proteins embedded in the membrane. The four blood type groups are distinguished from each other by the presence of structurally different sugar or carbohydrate portions.

Abbrevations:
Glc : Glucose;    N-acetylglucosamine : Nac-Glc ;   
Gal : Galactose    N-acetylgalactosamine : Nac-Gal ;    Fuc: Fucose

The enzymes for the synthesis of the carbohydrate chain in blood type O are common to all human beings. Individuals with blood group type A have an additional enzyme in their blood, which can attach a N-acetylgalactosamine to the galactose residue of the carbohydrate chain. Similar, People with blood group type B have an enzyme that can connect galactose to the galactose residue. People with blood group type AB can synthesize both carbohydrate chains, A and B. People with blood group type O have none of these enzymes and they can synthesize only the Fucose-Galactose-N-acetylglucosamine-Galactose-Glucose carbohydrate chain.

Compatibility of Blood Types

The additional sugars in type A , B and AB are called cell surface antigens, because they can trigger an immune response in individuals who have a blood group type in which these sugars are absent. People with blood group type O have carbohydrate chains without the antigens A (N-acetylgalactosamine) or B (galactose). They can receive only O-type blood, because they will develop antibodies against type A or B or AB antigens, which will attack the tranferred red blood cells and destroy them. Since O-type blood has no A or B component, it can be used to transfer to all other groups.

People with blood group type AB have no antibodies against antigens A and B and can receive blood from any ABO blood group.

People with blood group type A have no antibodies against antigen A, but can develop antibodies against antigen B. If they receive blood from type B or AB donors, the antibodies against B will destroy the transferred blood cells. Only type A or O can be transferred to type A blood.

People with blood type B have no antibodies against antigen B, but can develop antibodies against A. They cannot receive blood group type A or AB, only type B and O can be transferred.

Type Antibodies present
in blood		 Can receive
blood from
A Anti B A + O
B Anti A B + O
AB None A, B, O
O Anti A
Anti B		 O

Codominant Alleles

The gene - designated I - which encodes the enzymes that attach the sugars to the carbohydrates chain has three alleles. IA encodes the enzyme which adds N-acetylgalactoseamine to the carbohydrate chain. IB encodes the enzyme which adds galactose to the carbohydrate chain.The third allele i produces an enzyme that does not add any sugar to the carbohydrate chain. If IA and IB are present in an individual, both are expressed, i.e. the two alleles are codominant. The third allele IO is recessive, it is not expressed when paired with IA or IB. The table below shows the possible combinations of the three different alleles and the resulting ABO blood groups, depending on their pairing.

Possible alleles from mother Resulting
Blood Groups
A B O Type A
Possible
alleles
from
father		 A AA AB AO Type AB
B AB BB BO Type B
O AO BO OO Type O

Incomplete Dominance
Dominant heterocygotes resemble one parent. However, if one allele is not fully dominant a heterozygous phenotype may resemble an intermediate of both parents. Such a case is illustrated on a cross between a violet flowered and a white flowered plant.

The gametes can combine as shown in the Punnett square below.

Possible maternal
gametes
W W
Possible
paternal
gametes		 w W w W w All pink
w W w W w

W : allele for the incomplete dominant violet flower
w : allele for the recessive white flower
The F1 generation consists of identical individuals: It takes two WW alleles to produce a violet color. Because of incomplete dominance the genotype Ww appears pink

Self fertilization of the F1 generation
The gene pairs Ww will segregate during meiosis into gametes with dominant violet allele (W) and gametes with the recessive white allele (w)

Possible maternal
gametes
W w W W violet
Possible
paternal
gametes		 W W W W w W w pink
w W w w w w w white

Epistasis
Genes can interact with each other in a phenomenom called epistasis. Two alleles one one gene can mask the expression of another gene. For example the color of a Labrador retriever may vary between black (B) brown (b) and yellow. The two colors black (dominant) and brown (recessive) have a common gene locus, which is associated with production of the pigment melanin. At a different gene locus are two other alleles which determine whether or not the melanin pigment is deposited into dog's hairs. The dominant allele (E) allows deposition of the pigment, whereas the recessive allele (e) does not. If two recessive alleles (ee) are present no pigment is deposited and the dog is yellow. ( F1, F2 )

Possible maternal gametes in the F2 generation
BE B e bE b e
Possible
paternal
gametes
(F2)		 BE BBEE BBEe BbEE BbEe 9 black
Be BBEe BBee BbEe Bbee 4 yellow
bE BbEE BbEe bbEE bbEe 3 brown
be BbEe Bbee bbEe bbee

Sex linkage
Among the 23 pairs of human chromosomes, 22 pairs are of the same type in males are females. They are called the autosomes. Chromosomal pair 23 is different in females and consists of two X chromosomes and in males of an X and Y chromosome. They are the sex chromosomes and determine whether an individual is a male or female. There are probably about 200 genes associated with the X chromosome , but only a few of them are associated with female sexual traits, such as for example the distribution of body fat. Most of the genes on the X chromosome relate to non sexual traits.

Sex chromosome linked trait were first examined by Morgan, who studied fruit flies. He used a type which has red eyes. Through a mutation in this population some male white eyed flies appeared. After establishing true breeding white eyed male and female flies he performed a number of test crosses.
Homozygous red eyed female were paired with white eyed males. The F1 generation (offspring) had all red eyes, however some males of the F2 generation had white eyes. The figure below gives the genetic explanation of this test cross experiment.

In a second experiment pure bred white eyed female flies were crossbred with pure breeding red eyed male flies. The F1 generation consisted of red eyed females and and white eyed males and the F2 generation had the following distribution: red eyed females : white eyed females : red eyed males : white eyed males at a 1:1:1:1 ratio. The genetic explanation is shown below. Morgan concluded that the eye color is determined by a dominant allele (red) and a recessive allele (white) , located on the X chromosome, while the Y chromosome has no locus for eye color.

Genetic Maps
The tendency of genes located on the same chromosome to be found in the same gamete is called linkage. Crossing over during meiosis can break a linkage. If the genes are located very close to each other one a chromosome, the likelihood for them to end up in the same gamete is very high. However, if they are very far apart it is more likely that they get separated during crossing over and thus end up in different gametes, as show below

As shown above the separation of genes in meiosis by crossing over is more frequent for genes which are located further apart from each other than those who very close to each other. Thus the frequency of crossing over between two genes is a measure for how far they are separated from each other one a chromosome. If this frequency is known, a genetic map can be constructed where the frequency of crossing over can be related to the relative distance of genes from each other on a chromosome ( the higher the frequency of crossing over, the further apart are the genes on the chromosome and thus on the genetic map) pea chromosomes.

Genetic Diseases

Autosomal recessive alleles
Galactosemia: individuals with this disease can not break down lactose (milk sugar). This causes diarrhea and vomitting and if not treated death occurs in early childhood. An individual who is homozygous for the recessive allele will develop galactosemia. The Punnett squares below show the chnces of the offspring to have the condition if both parents are heterozygous for the alleles or if one parent is homozygous and the other is heterozygous. The recessive allele causing the disease is designated g, the dominant allele coding for the correct enzyme is designated G .

Heterozygous
Carrier (Gg)
Male Gametes
G g
Heterozygous
Carrier (Gg)		 Female
Gametes		 G GG Gg
g Gg gg

Only the offspring who has both recesive alleles (gg) will carry the disease. In case one parent has the disease (gg) and the other parent is heterozygous for the allele (Gg), there is a 50% chance for the offspring to have the condition.

Heterozygous
Carrier (Gg)
Male Gametes
G g
Homozygous
Carrier (gg)		 Female
Gametes		 g Gg gg
g Gg gg

Sickle cell anemia is another example for a faulty recessive allele. It codes for a faulty hemoglobin, which causes red blood cells to aggregate and assume a sickle shape. These aggregates are inefficient oxygen carriers, resulting in severe health problems for affected individual. The inheritance pattern is the same as discussed above.

Autosomal dominant alleles
Diseases carried through dominant alleles reduce the chances of being transmitted to the offspring, if they cause early death. One such condition which does not cause death is achondroplasia (dwarfism). The symptoms are short limbs and a short stature. The dominant allele causing the condition is designated A and the recessive allele is designated a. Individuals who are heterozygous (Aa) for the alleles will have the defect , only individuals with the homozygous alleles (aa) are non carriers. Below is the inheritance pattern for achondroplasia.

Affected Carrier (Aa)
Male Gametes
A a
Normal
Individual (aa)		 Female
Gametes		 a Aa aa
a Aa aa

The offspring who has the dominant alleles (A) will carry the condition. Only the offspring who has both recessive allele (aa) is normal. There is a 50% chance for the offspring to have the condition.
Another example for a diseases carried through dominant alleles is Huntington's disease. It is a progressive degeneration of the nervous system leading to death. The symptoms appear around the age of forty.

Sex linked recessive alleles
Hemophilia is disease which is inherited through a X chromosome linked recessive alleles. It codes for a protein which promotes blood clotting. Females who are heterozygous for this allele are not affected by the disease since the allele on second X chromosome is normal. Males who have inherited the defect allele contract the disease since males have only one X chromosome. Below is the inheritance pattern for hemophilia. The recessive, disease causing allele is designated x, it expresses a faulty bood clotting protein. The dominant allele is designated X, it expresses the a functioning blood clotting enzyme. The genetic inheritance pattern is shown below.

Normal Male
(XY)
Male Gametes
X Y
Female Carrier (Xx)
(not affected)		 Female
Gametes		 X XX XY
x Xx xY

The male offspring carrying the recessive allele (xY) has hemophilia. Examine the inheritance pattern of the offspring of an affected male (xY) and a healthy female (XX). ( Hemophilia )

Extra Autosomal Chromosome
If the chromosomal separation in meiosis is not completed, one gamete may end up with two chromosmes and a second one with none. This process is called non-disfunction and will result in a trisomic chromosome in the offspring. In most cases zygotes with a trisomic chromosome do not develop.

Down syndrome is the result of a non-disjunction of chromosome 21 in the female egg. Affected individuals have mild mental retardation, are shorter and have poor muscle tone. The condition is primarily caused by a non-disjunction of the female egg. The chances for Down syndrome are 1: 1700 in young women, but increase as high as 1:16 for women in their forties. The scheme illustrates the formation of a trisomic chromosome.

Extra Sex Chromosome
The non-disjunction of the X chromosomes result in a number of conditions as shown below.

Klinefelder syndrome (XXY) occurs in 1 out of 1000 male births. The male is sterile and has female body charateristics, also diminished mental capacities. The XXX condition produces a sterile female, which is otherwise normal. Female with Turner syndrome (XO) have only one X chromosome, they are of short stature and are mentally retarted. A YO male does not develop, since the X chromosome is missing.

Non-disjunction of the Y chromosomes results in the XYY condition. One in 1000 males has this condition. Males are taller and are mildly retarted. There is also an interesting finding that XYY male are more prone to commit crimes that their XY conterparts.