I.

Following the Inheritance of One Gene—Segregation

 was the first thinker to probe the underlying rules of logic that make it possible to
predict inheritance of specific traits. In a series of clever breeding experiments in pea plants,
Mendel described units of inheritance that pass traits from generation to generation.

 He called these units “ .” He could not see them, but he inferred their existence from
the appearances of his plants. Although Mendel knew nothing of DNA, chromosomes, or cells,
his “laws” of inheritance have not only stood the test of time, but explain trait transmission in
any diploid species.

 Mendel the Man The son of a farmer and grandson of a gardener, Mendel learned early how to
tend fruit trees. At age 10 he left home to attend a special school for bright students, supporting
himself by tutoring.

 He eventually became a priest at an atypical Augustinian monastery where the priests were
teachers and did research in natural science. Here, Mendel learned how to artificially pollinate
crop plants to control their breeding.

 At age 29, he was such an effective substitute teacher that he was sent to earn a college degree.
At the , courses in the sciences and statistics fueled his interest in plant breeding
and got him thinking about a question that had confounded other plant breeders—why did
certain traits disappear in one generation, yet reappear in the next?

 From to , Mendel crossed and cataloged traits in plants, through several

generations. He deduced that consistent ratios of traits in the offspring indicated that the plants
transmitted distinct units.

 He derived two hypotheses to explain how inherited traits are transmitted. Mendel described
his work to the Brno Medical Society in 1865 and published it in the organization’s journal the
next year. The remarkably clear paper discussed plant hybridization, the reappearance of traits
in the third generation, and the joys of working with peas.

 It took years for Mendel’s findings to be recognized. Shortly after his treatise was published in
English in 1901, three botanists (Hugo DeVries, Karl Franz Joseph Erich Correns, and Seysenegg
Tschermak) independently rediscovered the laws of inheritance.

 Once they read Mendel’s paper, they credited him. Mendel came to be regarded as the
“ “.

 In the twentieth century, researchers discovered the molecular basis of some of the traits that
Mendel studied. “Short” and “tall” plants reflect expression of a gene that enables a plant to
produce the hormone , which elongates the stem. One tiny change to the DNA, and a
short plant results.

 Likewise, “round” and “wrinkled” peas arise from the R gene, whose encoded protein connects
sugars into branching polysaccharide molecules. Seeds with a mutant R gene cannot attach the
sugars. As a result, water exits the cells, and the peas wrinkle.
 Peas are ideal for probing heredity because they are easy to grow, develop quickly, and have many
traits that take one of two easily distinguishable forms. Figure 4.3 illustrates the seven traits that
Mendel followed through several pea generations.

 When analyzing genetic crosses, the first generation is the , or P 1;

 the second generation is the or F 1;

 the next generation is the , or F 2, and so on.

 Mendel’s first experiments dealt with single traits with two expressions, such as “short” and “tall.”
He set up all combinations of possible artificial pollinations, manipulating fertilizations to cross tall
with tall, short with short, and tall with short plants.

 This last combination, plants with one trait variant crossed to plants with the alternate,
produces , which are offspring that inherit a different gene variant (allele) from each parent.

 Mendel noted that short plants crossed to other short plants were “ ,” always producing
short plants.
 The crosses of tall plants to each other were more confusing. Some tall plants were true-breeding,
but others crossed with each other yielded short plants in about one-quarter of the next generation.
It appeared as if in some tall plants, tallness could mask shortness.

 One trait that masks another is said to be ; the masked trait is . Mendel conducted
up to 70 hybrid crosses for each of the seven traits. Because one trait is followed and the parents
are hybrids, this is called a cross.
 When Mendel allowed the non-true-breeding tall plants—monohybrids—to self-fertilize, the
progeny were in the ratio of one-quarter short to three-quarters tall plants ( figure 4.4 ). In
further crosses, he found that two-thirds of the tall plants from the monohybrid F 1cross were
non-true-breeding, and the remaining third were true-breeding. In these experiments, Mendel
confirmed that hybrids hide one expression of a trait—short, in this case—which reappears
when hybrids are self-crossed.
 He tried to explain how this happened:

 Gametes distribute “elementen” because these cells physically link generations. Paired sets of
elementen separate as gametes form.

 When gametes join at fertilization, the elementen combine anew.

 Mendel reasoned that each elementen was packaged in a separate gamete.

 If opposite-sex gametes combine at random, he could mathematically explain the different

ratios of traits produced from his pea plant crosses. Mendel’s idea that elementen separate in
the gametes would later be called the law of segregation.

 When Mendel’s ratios were demonstrated in several species in the early 1900s, just when
chromosomes were being discovered, it became apparent that elementen and chromosomes
had much in common.

 Both paired elementen and pairs of chromosomes separate at each generation and are
transmitted—one from each parent—to offspring.

 Both are inherited in random combinations. Chromosomes provided a physical mechanism for
Mendel’s hypotheses.

 In 1909, English embryologist William Bateson renamed Mendel’s elementen (Greek for
“give birth to”).
Terms and Tools to Follow Segregating Genes
 An individual with two identical alleles for a gene is for that gene.
 An individual with two different alleles is
 When considering a gene with two alleles, the dominant one is shown as a capital letter and the
recessive with the corresponding small letter.
 If both alleles are recessive, the individual is homozygous recessive, shown with two small
letters.
 An individual with two dominant alleles is homozygous dominant, and has two capital letters.
 One dominant and one recessive allele, such as Tt for non-true-breeding tall pea plants,
indicates heterozygotes.
 An organism’s appearance does not always reveal its alleles. Both a TT and a Tt pea plant are
tall, but TT is a and Tt a .
 The describes the organism’s alleles, and the describes the outward
expression of an allele combination
 A wild type phenotype is the most common expression is the most common expression of a
particular allele combination in a population; it may be recessive or dominant.
 A mutant phenotype is a variant of a gene’s expression that arises when the gene undergoes
change, or mutation.

 Because two of the four possible gamete combinations produce a heterozygote, and each of the
others produces a homozygote , the genotypic ratio expected of a monohybrid cross is 1TT: 2Tt;
1tt (1:2:1). The corresponding phenotypic ratio is three tall plants to one short plant, a 3:1 ratio.
 Experimental crosses yielded numbers of offspring that approximate these ratios. Mendel
distinguished the two genotypes resulting in tall progeny— TT from Tt —with more crosses (
figure 4.7 ).

 He bred tall plants of unknown genotype with short ( tt ) plants. If a tall plant crossed with a tt
plant produced both tall and short progeny, it was genotype Tt; if it produced only tall plants, it
must be TT.Crossing an individual of unknown genotype with a homozygous recessive individual
is called a test cross.

 The logic is that the homozygous recessive is the only genotype that can be identified by its
phenotype—that is, a short plant is always tt. The homozygous recessive is a “known” that can
reveal the unknown genotype of another individual to which it is crossed.
Key Concepts
1. Mendel deduced that elementen for height segregate, then combine at random with those from
the opposite gamete at fertilization.
2. A homozygote has two identical alleles, and a heterozygote has two different alleles. The allele
expressed in a heterozygote is dominant; the allele not expressed is recessive.
3. A monohybrid cross yields a genotypic ratio of 1:2:1 and a phenotypic ratio of 3:1.
4. Punnett squares display expected genotypic and phenotypic ratios among progeny.
5. A test cross uses a homozygous recessive individual to reveal an unknown genotype.

II. Single-Gene Inheritance in Humans

 Mendel’s first law addresses traits determined by single genes. Inheritance of single genes is also
called Mendelian, or inheritance.

 Because of the rarity of single-gene diseases, getting an accurate diagnosis can be difficult because
physicians are unfamiliar with the phenotype.

 Reading 4.1 describes a few unusual single-gene traits.

  Single-gene inheritance is much more complicated than it might appear from considering such
obvious traits as green or yellow pea color.

 Sequencing the human genome and using SNPs (points in the genome where people vary) to
catalog inherited variation in genome-wide association studies have revealed that the
phenotypes associated with single genes are influenced by other genes as well as by
environmental factors.

Modes of Inheritance
 Modes of inheritance are rules that explain the common patterns of single-gene transmission.
 They are derived from Mendel’s laws.
 Knowing mode of inheritance makes it possible to calculate the probability that a particular
couple will have a child who inherits a particular condition.
 The way that a trait is passed depends on whether the gene that determines it is on an
autosome or on a sex chromosome, and whether the particular allele is recessive or dominant.
 In autosomal dominant inheritance, a trait can appear in either sex because an autosome carries
the gene. If a child has the trait, at least one parent also has it.
 That is, autosomal dominant traits do not skip generations. If no offspring inherit the trait in one
generation, its transmission stops because the offspring can pass on only the recessive form of
the gene.
 An autosomal recessive trait can appear in either sex. Affected individuals have a homozygous
recessive genotype, whereas in heterozygotes (carriers) the wild type allele masks expression of
the mutant allele.

The Punnett square in

figure 4.9 depicts
inheritance of an
autosomal dominant trait
or condition and table 4.2
summarizes the criteria.
Huntington disease is an autosomal dominant condition.

The Punnett square in figure

4.10 depicts inheritance of
an autosomal recessive trait
or condition and table 4.3
summarizes the criteria.
 Sean P., like Henry, doesn’t actually have symptoms of a genetic disease, but he has lived with one in his
family all his life. Although he and his parents are healthy, his younger sister Ellen has cystic fibrosis (CF).
Sean remembers looking forward to the arrival of the baby when he was in kindergarten, but never
expected the extent of her health problems.
Ellen couldn’t gain weight, and she seemed always to have respiratory infections and difficulty
breathing. When bronchitis turned into pneumonia when she was only 8 months old, her pediatrician
ordered a test for CF—Ellen indeed had a classic case, with two copies of the most common mutation.
That was several years ago. Today, Sean’s mother’s carrier status would have been picked up during
pregnancy, and then his father tested, and he, too, would have been found to be a carrier. Then
newborn screening would have revealed that Ellen had inherited the mutation from both parents, and
treatment begun—enzymes to help digestion and breathing, and antibiotics to prevent infection. The
greatest impact on the children was the twice-daily “airway clearance” respiratory therapy that the
parents took turns performing. At first Sean thought that they were punishing his baby sister when they
turned her in different positions and hit her back, but quickly realized that they were shaking free the
thick mucus that was clogging her lungs (figure 4.2). Ellen’s childhood was rough, with frequent hospital
stays and constant vigilance to keep her free of infection. No one else in the family had the disease. One
summer, Sean went to a summer camp for CF families, and it was there that he realized that he could be
a carrier, like his parents. So, a few years later, he took a CF test at the campus health center, and
learned that he, too, is a carrier.

 HD is autosomal dominant, which means that it affects both sexes and appears every generation. In
contrast, CF is autosomal recessive, which means that it affects both sexes and can skip generations
through carriers. Henry’s sister became ill because only one mutant gene is necessary for this to
happen in an autosomal dominant disease. Sean will not become ill because two mutations are
required to inherit an autosomal recessive disease.
 Most autosomal recessive conditions appear unexpectedly in families. However, a situation in which
an autosomal recessive condition is more likely to recur is when blood relatives have children
together.
 The higher risk of having a child with a particular autosomal recessive condition is because the
related parents may carry the same alleles inherited from an ancestor that they have in common,
such as a grandparent.
 Marriage between relatives introduces consanguinity, which means “shared blood”—a figurative
description, since genes are not passed in blood
 Logic explains why consanguinity raises risk of inheriting autosomal recessive diseases.
 An unrelated man and woman have eight different grandparents, but first cousins have only six,
because they share one pair through their parents, who are siblings.
 That is, the probability of two relatives inheriting the same disease-causing recessive allele is greater
than that of two unrelated people having the same allele by chance

Solving a Problem-Segregation
1. List all possible genotypes and phenotypes for the trait.
2. Determine the genotypes of the individuals in the first (P 1 ) generation. Use information about those
individuals’ parents.
3. After deducing genotypes, derive the possible alleles in gametes each individual produces.
4. Unite these gametes in all combinations to reveal all possible genotypes. Calculate ratios for the F 1
generation.
5. To extend predictions to the F 2 generation, use the genotypes of the specified F 1 individuals and
repeat steps 3 and 4.

 As an example, consider curly hair, depicted in figure 4.10

 If C is the dominant allele, conferring curliness, and c is the recessive allele, then both CC and Cc
genotypes result in curly hair.
 A person with a cc genotype has the straight hair phenotype.
 Wendy has beautiful curls, and her husband Rick has straight hair.
 Wendy’s father is bald, but once had curly hair, and her mother has stick-straight hair.
 What is the probability that Wendy and Rick’s child will have straight hair? Steps 1 through 5 solve
the problem:
1. State possible genotypes: CC, Cc = curly; cc = straight

2. Determine genotypes: Rick must be cc, because his hair is straight. Wendy must be Cc, because
her mother has straight hair and therefore gave her a c allele.

3. Determine gametes: Rick’s sperm carry only c. Half of Wendy’s oocytes carry C, and half carry c.

4. Unite the gametes:

5. Conclusion: Each child of Wendy and Rick has a 50 percent chance of having curly hair ( Cc ) and a 50
percent chance of having straight hair ( cc ).
Problem no. 2

Albinism- is a congenital disorder characterized by the complete or partial absence of pigment in the
skin, hair and eyes. It is due to the absence or defect of tyrosinase, a copper-containing enzyme involved
in the production of melanin.

Autosomal Recessive Disorder

 a sufferer or the one having the disorder must inherit 2 recessive alleles from each of his
parents.

 Wendy and Rick have heterozygous alleles for Albinism.

 What is the probability that Wendy and Rick’s child will express the disorder, albinism?

 Follow steps 1 to 5.

1. AA-homozygous dominant= Healthy

Aa-heterozygote= healthy (Carrier)

aa- homozygous recessive= only way one can inherit an autosomal recessive disorder=
ALBINISM

2. Rick and Wendy are both heterozygotes. So they both have the Aa genotype.

3. Half of Rick’s sperm carry A and half carry a. Half of Wendy’s oocyte also carry A and half carry
a.

4. Unite the gametes.

5. conclusion: each of Rick and Wendy’s child has 25% chance of being perfectly healthy; 50%
chance of being a carrier; 25% chance of expressing albinism.

Problem no. 3

HUNTINGTON’S Disease-is a fatal genetic disorder that causes the progressive breakdown of nerve cells
in the brain. It deteriorates a person’s physical and mental abilities usually during their prime working
years and has no cure.

Autosomal Dominant Disorder

 Individuals must at least inherit only 1 dominant allele to have the disorder

 Ann (Henry and Sue’s mother) has heterozygous alleles for HD.

 Robert ( Ann’s Husband/Henry and Sue’s Father) is perfectly healthy; free of HD

 What is the probability that Henry and Sue will inherit Huntington’s Disease?
1. HH=homozygous dominant, will not be able to live long because he/she inherited 2 dominant alleles
which means he/she has the severe version of the disorder; Hh=heterozygotes, they still have the
disease but the moderate version of it, usually live until reproductive age; hh=homozygous
recessive, healthy.
2. Ann is heterozygote therefore she has the Hh genotype; Robert is healthy therefore he has the hh
genotype.
3. Half of Ann’s oocyte carry H and have carry h; Robert’s sperm carry only c allele.

4. Unite the gametes.

5. Conclusion: each of Robert and Ann’s child/children has 50% chance of having HD; and 50% chance
of being healthy/HD free

Autosomal Recessive Disorders Autosomal Dominant Disorders

Cystic Fibrosis Huntington’s disease
Phenylketonuria(PKU) Neurofibromatosis
Galactosemia Von Willebrand Disease
Wilson’s Disease Mafran Syndrome
Hemochromatosis Familial Hypercholesterolemia
Glycogen Storage Diseases Hereditary Spherocytosis
Following the Inheritance of Two Genes—Independent Assortment
 Mendel’s Second Law
The second law, , states that for two genes on different chromosomes,
the inheritance of one does not influence the chance of inheriting the other. The two genes thus
“independently assort” because they are packaged into gametes at random ( figure 4.11).

• Mendel looked at seed shape, which was either round or wrinkled (determined by the R gene),
and seed color, which was either yellow or green (determined by the Y gene).
• When he crossed true-breeding plants that had round, yellow seeds to true-breeding plants that
had wrinkled, green seeds, all the progeny had round, yellow seeds.
• These offspring were double heterozygotes, or dihybrids, of genotype RrYy. From their
appearance, Mendel deduced that round is dominant to wrinkled, and yellow to green.
• Next, he self-crossed the dihybrid plants in a dihybrid cross, so named because two genes and
traits are followed. Mendel found four types of seeds in the next, third generation: 315 plants
with round, yellow seeds; 108 plants with round, green seeds; 101 plants with wrinkled, yellow
seeds; and 32 plants with wrinkled, green seeds. These classes occurred in a ratio of 9:3:3:1.
• Mendel then took each plant from the third generation and crossed it to plants with wrinkled,
green seeds (genotype rryy ).
• These test crosses established whether each plant in the third generation was true-breeding for
both genes (genotypes RRYY or rryy), true-breeding for one gene but heterozygous for the other
(genotypes RRYy, RrYY, rrYy, or Rryy ), or heterozygous for both genes (genotype RrYy ).
• Mendel could explain the 9:3:3:1 proportion of progeny classes only if one gene does not
influence transmission of the other. Each parent would produce equal numbers of four different
types of gametes: RY, Ry, rY,and ry.
• Note that each of these combinations has one gene for each trait. A Punnett square for this
cross shows that the four types of seeds:
1. round, yellow ( RRYY, RrYY, RRYy, and RrYy )
2. round, green ( RRyy and Rryy )
3. wrinkled, yellow ( rrYY and rrYy ) and
4. wrinkled, green (rr yy )are present in the ratio 9:3:3:1, just as Mendel found ( figure 4.12 ).