Molecular Genetics Chapter 3: Mendelian Genetics

Mendal's fourth postulate: Independent Assortment

During gamete formation, segregating pairs of unit factors (Remember unit factors are genes on chromosomes) assort independently of each other. This postulate stipulates that segregation of any pair of unit factors occurs independently of all others. As a result of random segregation, each gamete receives one member of every pair of unit factors. For one pair, whichever unit factor is received does not influence the outcome of segregation of any other pair. Thus, according to the postulate of independent assortment, all possible combinations of gametes should be formed in equal frequency.

Each species possesses a specific number of chromosomes in each somatic cell nucleus. T/F

T For diploid organisms, this number is called the diploid number (2n).

T/F Mendel demonstrated that the processes of segregation and independent assortment also apply to three pairs of contrasting traits

T this is called a trihybrid cross

Figure 3.8 trihybrid cross gamete formation

The allele pairs of theoretical contrasting traits are represented by A, a, B, b, C, c. In the cross between AABBCC and aabbcc individuals, the F1 individuals are heterozygous for all three gene pairs. Their genotype AaBbCc results in the phenotypic expression of the dominant A, B, and C traits. When the F1 individuals serve as parents, each produces eight different gametes in equal frequencies. At this point we could construct a Punnett square with 64 boxes but this is tedious and we will do something else described next.

A good review and read on chromosomes and what we have talked about.

The currently accepted concept is that a chromosome is composed of a large number of linearly ordered, information-containing genes. Mendel's paired unit factors (which determine tall or dwarf steams, for example) actually constitute a pair of genes located on one pair of homologous chromosomes. The location on a given chromosome where any particular gene occurs is called its Locus (pl. loci). The different alleles of a given gene (for example, G and g) contain slightly different genetic information (green or yellow) that determines the same character (seed color in this case). Keep in mind that although we have examined only genes with two alternative alleles, most genes have more than two allelic forms.

Figure 3.11 conventions commonly encountered in human pedigrees (the pedigree key explained)

When a pedigree traces only a single trait, the circles, squares, and diamonds are shaded if the phenotype being considered is expressed and unshaded if not. - In some pedigrees, those individuals that fail to express a recessive trait but are known with certainty to be heterozygous carriers have a shaded dot within their unshaded circle or square.

Mendel's "Unit factors" are really _______ located on ________________.

genes located on homologous pairs of chromosomes.

The genotype designates the......

genetic makeup of an individual for the trait or traits it describes

For diploid organisms, during the process of meiosis, the number is precisely ____________

halved (n), and when the two gametes combine during fertilization, the diploid number is reestablished.

When the alleles are different (Dd) we use the terms _____________ and ______________

heterozygous and heterozygote

Mendal's simplest crosses involved only one pair of contrasting traits. Each such experiment is called a _______________ cross

monohybrid cross

Following independent segregation of each pair of homologs, each gamete receives ________ member from each pair of chromosomes.

one All possible combinations are formed with equal probability.

The traditional way to study inheritance in humans has been to construct a family tree, indicating the presence or absence of the trait in question for each member of each generation. Such a family tree is called a ___________________

pedigree By analyzing a pedigree, we may be able to predict how the trait under study is inherited. For example, is it due to a dominant or recessive allele?

The physical expression of a trait is the ________ of the individual

phenotype

T/F When mendal began his studies of inheritance using the garden pea, chromosomes and the role and mechanism of meiosis were totally unknown

t, nevertheless, he determined that discrete units of inheritance existed and predicted their behavior in the formation of gametes.

Chromosome theory of inheritance

the idea that the genetic material in living organisms is contained in chromosomes

product law of probabilities

the probability of two or more independent events occurring simultaneously is equal to the product of their individual probabilities. For example, the probability of an F2 plant having yellow and round seeds is (3/4)(3/4), or 9/16 because 3/4 of all F2 plants should be yellow and 3/4 of all F2 plants should be round.

Mendel followed seven visible features ( we refer to them as characters, or characteristics), each represented by two contrasting forms, or ______________

traits

Testcross

Used to discover the unknown genotype of an organism displaying the dominant phenotype. ( The genotype could be AA or Aa) - In a testcross, the organism expressing dominant phenotype but having an unknown genotype is crossed with a known homozygous recessive individual (aa). The image shows the results and determination of the genotype based on the results.

Practice using the forked-line method to determine genotypic and phenotypic ratios of trihybrid and dihybrid crosses. There are problems in the book.

Yes

Every individual has ______ alleles per gene. One from _________ and the other from __________

2 alleles one from the mother and one from the fther

Tay-Sachs disease (TSD)

A devastating recessive disorder involving unalterable destruction of the central nervous system. Typical of rare autosomal recessive disorders, two unaffected heterozygous parents, who most often have no family history of the disorder, have a probability of one in four of having a Tay-Sachs child.

How is a monohybrid cross conducted

A monohybrid cross is made by mating true-breeding individuals from two parent strains, each exhibiting one of the two contrasting traits of the character under study.

How did Mendal prove that the results of his monohybrid crosses were not sex dependent?

By using reciprocal crosses

example of the sum law

For example, what is the probability of tossing our penny and nickel and obtaining one head and one tail? In such a case, we do not care whether it is the penny or the nickel that comes up heads, provided that the other coin has alternative outcome. As we saw in the example of product law, there are two ways in which the desired outcome can be accomplished, each with a probability of 1/4. Thus, according to the sum law, the overall probability in our example is equal to: (1/4) + (1/4) = 1/2 -one half of all two-coin tosses are predicted to yield the desired outcome

Briefly explain the results of the monohybrid crosses in relation to their traits in the specified generations

For the character of interest, all F1 offspring expressed the same trait exhibited by one of the parents (the dominant trait) but in the F2 offspring, an approximate ratio of 3:1 was obtained. That is, three- fourths looked like the F1 plants, while one fourth exhibited the contrasting trait, which had disappeared in the F1 generation (the trait which disappears in the F1 generation only to reappear in a 25% ratio in the F2 generation is the recessive trait)

When alleles are written in pairs to represent the two genes present for a trait in an individual (DD, Dd or dd), the resulting symbol is the _____________

Genotype Uppercase- dominant lowercase- recessive

The protein product involved in TSD has been identified, and we now have a clear understanding of the underlying molecular basis of the disorder. TSD results from the loss of activity of a single enzyme, ________________

Hexosaminidase (Hex-A).

What are reciprocal crosses

In each monohybrid cross, the F1 and F2 patterns of inheritance were similar regardless of which P1 plant served as the source of pollen (sperm) and which served as the source of the ovum (egg). The crosses could be made either way- pollination of dwarf plants by tall plants or vice versa. Crosses made in both these ways are called reciprocal crosses

The genotypes and phenotypes resulting from combining gametes during fertilization can be easily visualized by constructing a diagram called a __________________

Punnet Square

If we want to calculate the probability when the possible outcomes of two events are independent of one another but can be accomplished in more than one way, we can apply the ___________.

Sum law The sum law states: the probability of obtaining any single outcome, where that outcome can be achieved by two or more events, is equal to the sum of the individual probabilities of all such events.

T/F proteins are the end products of the expression of most genes

T

an important point to remember when dealing with probability

The predictions of possible outcomes are based on large sample sizes. The deviation from the predicted ratio in smaller sample sizes is attributed to chance and the impact of deviation due strictly to chance diminishes as the sample size increases.

albinism

a trait that demonstrates autosomal recessive inheritance -synthesis of the pigment melanin is obstructed

the forked-line method can be used to solve crosses involving any number of gene pairs, provided that __________________

all gene pairs assort independently from each other (we will see later that gene pairs do not always assort with complete independence, However, it appeared to be true for all of Mendel's characters)

Autosomal

all the other genes in the body that are not sex-linked.

For any given character, such as plant height, the phenotype is determined by alternative forms of a single gene, called _____________

alleles

Mendal also designed experiments in which he examined two characters simultaneously. Such a cross, involving two pairs of contrasting traits, is a _______________.

dihybrid cross

T/F independent assortment does not lead to genetic variation

false, Independent assortment leads to extensive genetic variation

One member of each pair of homologs is derived from the ____________________ whereas the other comes from the ___________________

maternal parent paternal parent

In pedigrees, the individual whose phenotype first brought attention to the family is called the ________ and is indicated by an arrow connected to the designation p.

proband

Hybridize or cross breed

produce (an animal or plant) by mating or hybridizing two different species, breeds, or varieties.

T/F Traits such as tall or dwarf are physical expressions of the information contained in unit factors

t

Members of each pair of homologs separate or ____________ during gamete formation.

segregate

Mendel's unit factors in pairs are most accurately known to be __________.

two alleles on paternal and maternal homologs

Mendel's success where others had failed can be attributed, at least in part, to his elegant experimental design and analysis. Explain some of the ideas of his experiment that made it unique.

-The organism he chose, a pea plant, is very abundant and inexpensive - The pea plant is very easy to grow and hybridize artifically - The pea plant is self-fertilizing in nature, but is easy to cross-breed experimentally -he restricted his examination to one or very few pairs of contrasting traits in each experiment. -Crossed true-breeding strains (in true-breeding strains, traits are appeared unchanged generation after generation) True breeders are also AA or aa not Aa

Recall that genetic ratios-for example, 3/4 tall:1/4 dwarf- are most properly though of as probabilities. Probabilities range from _____ where an event is certain not to occur, to ______ where an event is certain to occur

0.0 1.0

The three criteria to classify two chromosomes as a homologous pair

1. During mitosis and meiosis, when chromosomes are visible in their characteristic shapes, both members of a homologous pair are the same size and exhibit identical centromere locations. The sex chromosomes ( the x and y chromosomes in most mammals) are an exception. 2. During early stages of meiosis, homologous chromosomes form pairs, or synapse. 3. Although it is not generally visible under the microscope, homologs contain the identical linear order of gene loci.

Mendel's First Three Postulates

1. Unit factors in Pairs - Genetic characters are controlled by unit factors existing in pairs in individual organisms. In the monohybrid cross involving tall and dwarf stems, a specific unit factor exists for each trait. Each diploid individual receives one factor from each parent. Because the factors occur in pairs, three combinations are possible: two factors for tall stems, two factors for dwarf stems, or one of each factor. Every individual possesses one of three combinations, which determines stem height in this example. 2. Dominance/Recessiveness -When two unlike unit factors responsible for a single character are present in a single individual, one unit factor is dominant to the other, and the other is said to be recessive. In the monohybrid crosses, the trait expressed in the F1 generation is controlled by the dominant unit factor. The terms dominant and recessive are also used to designate traits. In this case, tall stems are said to be dominant over recessive dwarf stems. 3. Segregation - During the formation of gametes, the paired unit factors separate, or segregate, randomly so that each gamete receives one or the other with equal likelihood. If an individual contains a pair of like unit factors (e.g., both specific for tall), then all its gametes receive one of that same kind of unit factor (in this case, tall). If an individual contains unlike factors (e.g., one for tall and one for dwarf), then each gamete has a 50% probability of receiving either the tall or the dwarf unit factor.

The punnet square in figure 3.7 shows how independent assortment works in the formation of the F2 generation. Explain this (very important to read all)

Examine the formation of gametes by the F1 plants; segregation prescribes that every gamete receives either a G or a g allele and a W or a w allele. Independent assortment stipulates that all four combinations (GW, Gw, gW and gw) will be formed with equal probabilities. In every F1xF1 fertilization event, each zygote has an equal probability of receiving one of the four combinations from each parent. If many offspring are produced 9/16 have yellow seeds, round seeds, 3/16 have yellow, wrinkled seeds, 3/16 have green, round seeds, and 1/16 have green, wrinkled seeds, yielding what is designated as Mendel's 9:3:3:1 dihybrid ratio.

t/f by reading the genotype, we know the phenotype of the individual and vice versa

False, If we know the genotype we can determine(or is it predict bc environment ask) the phenotype but if we know the phenotype we cannot necessarily determine the genotype. (cant distinguish between AA or Aa)

It is much less difficult to consider each contrasting pair of traits separately and then to combine these results by using the _________________

Forked-line method (also called a branch diagram) The forked-line method relies on the simple application of the laws of probability established for the dihybrid cross. Each gene pair is assumed to behave independently during gamete formation.

Independent assortment leads to genetically dissimilar gametes. Why?

Genetic variation results because two members of any homologous pair of chromosomes are rarely, if ever, genetically identical. As the maternal and paternal members of all pairs are distributed to gametes through independent assortment, all possible chromosome combinations are produced, leading to extensive genetic diversity.

What happens due to the loss of Hex-A and what is its normal function

Hex-A is normally found in lysosomes within cells, and is needed to break down the ganglioside GM2, a lipid component of nerve cell membranes. Without functional Hex-A, gangliosides accumulate within neurons in the brain and cause deterioration of the nervous system. Heterozygous carries of TSD with one normal copy of the gene produce only about 50 percent of the normal amount of Hex-A, but they show no symptoms of the disorder. The observation that the activity of only one gene (one wild-type allele) is sufficient for the normal development and function of the nervous system explains and illustrates the molecular basis of recessive mutations. Only when both genes are disrupted by the mutation is the mutant phenotype evident. Cool note: The responsible gene for TSD is located on chromosome 15 and codes for the alpha subunit of the Hex-A enzyme. More than 50 different mutations within the gene have been identified that lead to TSD phenotypes.

When a mutation is dominant, and a single copy is sufficient to produce a mutant phenotype, how does this affect homozygotes? Give an example of this

Homozygotes (AA in this case) are likely to be even more severely, perhaps even failing to survive. An example of this is familial hypercholesterolemia. Heterozygotes display a defect in their receptors for low density lipoproteins, the so-called LDLs (known populary as "bad cholesterol"). As a result, too little cholesterol is taken up by cells from the blood, and elevated plasma levels of LDLs result. Without intervention, such heterozygous individuals usually have heart attacks during the fourth decade of their life, or before. While heterozygotes have LDL levels about double that of a normal individual, rare homozygotes have been detected. They lack LDL receptors altogether, and their LDL levels are nearly ten times above the normal range. They are likely to have a heart attack very early in life, even before age 5, and almost inevitable before they reach the age of 20.

In figure 3.5 Instead of crossing one P1 parent with both dominant traits (yellow, round) to one with both recessive traits (green and wrinkled), plants with yellow, wrinkled seeds and crossed with those with green, round seeds. In spite of the change in the P1 phenotypes, both the F1 and F2 results remain unchanged. Why?

Independent assortment, which will be explained later in the quizlet

How do these postulates provide a suitable explanation for the monohybrid crosses? Use the tall/dwarf cross to illustrate.

Mendel reasoned that P1 tall plants contained identical paired unit factors, as did the P1 dwarf plants. The gametes of tall plants all receive one tall unit factor as a result of segregation and the gametes of dwarf plants receive one dwarf unit factor. Following fertilization of the two gametes, all F1 plants receive one unit factor from each parent- a tall factor from one and a dwarf from the other but since the tall is dominant to dwarf, the F1 generation plants are all tall. When F1 plants form gametes, the postulate of segregation demands that each gamete randomly receives either the tall or dwarf unit factor. Following random fertilization events during F1 selfing, four F2 combinations will result with equal frequency -Tall/Tall -Tall/Dwarf -Dwarf/Tall -dwarf/dwarf Combination 1 and 4 result in tall and dwarf plants respectively and according to postulate 2 combination 2 and 3 will yield tall plants because tall is dominant. Therefore the F2 is predicted to consist of 3/4 tall and 1/4 dwarf or a ratio of 3:1 which was observed by mendal

Initially, we examine the first generation of offspring of these crosses and then consider the offspring of selfing or of self-fertilization of individuals from this first generation. The original parents constitute the ____ or ______________; their offspring are the _____ or ________________; the individuals resulting from the selfed F1 generation are the _____ or ____________ and so on

P1 or parental generation F1 or first filial generation F2 or second filial generation

These numbers above (3/4 relating to 12/16 and 1/4 relating to 4/16) demonstrate that the two pairs of contrasting traits are inherited independently, so we can predict the frequencies of all possible F2 phenotypes by applying the _________________

Product law of probabilities

Figure 3.12 (b) illustrates the pattern of inheritance for a trait such as Huntington disease, which is caused by an autosomal dominant allele.

The key to identifying a pedigree that reflects a dominant trait is that all affected offspring will have a parent that also expresses the trait. It is also possible, by chance, that none of the offspring will inherit the dominant allele. If so, the trait will cease to exist in future generations. When a given autosomal dominant disease is rare within the population, and most are, then it is highly unlikely that affected individuals will inherit a copy of the mutant gene from both parents. (the non affected parent is aa) Therefore, in most cases, affected individuals are heterozygous for the dominant allele. As a result, approx 1/2 of the offspring inherit it which is shown true in the pedigree.

Figure 3.12 (a) pedigree demonstrating the autosomal recessive inheritance of albinism including an an in-depth analysis of it.

The male parent of the first generation (I-1) is affected. Characteristic of a situation in which a parent has a rare recessive trait, the trait "disappears" in the offspring of the next generation. Assuming recessiveness, we might predict that the unaffected female parent (I-2) is a homozygous normal individual because none of the offspring show the disorder. Had she been heterozygous, one-half of the offspring would be expected to exhibit albinism, but none do. However, such a small sample (three offspring) prevents our knowing for certain. Further evidence supports the prediction of a recessive trait. If albinism were inherited as a dominant trait, individual II-3 would have to express the disorder in order to pass it to his offspring (III-3 and III4), but he does not. Row III provides further evidence that albinism is inherited recessively. If it is, parents II-3 and II-4 are both heterozygous, and approx one-fourth of their offpsring should be affected. Two of the six offspring do show albinism. This deviation from the expected ratio is not unexpected in crosses with few offspring. Once we are confident that albinism is inherited as an autosomal recessive trait, we could portray the II-3 and II-4 individuals with a shaded dot within their larger square and circle.

Product law definition and penny example.

The product law states that the probability of two or more independent events occurring simultaneously is equal to the product of their individual probabilities. Illustrating the product law: Consider the possible results if you toss a penny (P) and a nickel (N) at the same time and examine all combinations of heads (H) and tails(T). (P(H):N(H))=(1/2)(1/2)=1/4 (P(T):N(H))=(1/2)(1/2)=1/4 (P(H):N(T))=(1/2)(1/2)=1/4 (P(T):N(T))=(1/2)(1/2)=1/4 The probability of obtaining a head or a tail in the toss of either coin is 1/2 and is unrelated to the outcome for the other coin. Thus, all four possible combinations are predicted to occur with equal probability

Figure 3.5 F1 and F2 results of a Mendal dihybrid cross in which the plants on the top left with yell, round seeds are crossed with plants having green, wrinkled seeds, and the plants on the top right with yellow, wrinkled seeds are crossed with plants having green, round seeds.

The results show that the F1 offspring are all yellow and round. It is therefore apparent that yellow is dominant to green and that round is dominant to wrinkled. When the F1 individuals are selfed, approx 9/16 of the F2 plants express the yellow and round traits, 3/16 express yellow and wrinkled, 3/16 express green and round, and 1/16 express green and wrinkled

Later on, investigators with access to cytological data were able to relate their own observations of chromosome behavior during meiosis and Mendel's principles of inheritance. Once this correlation was recognized, Mendel's postulates were accepted as the basis for the study of what is known as _______________________

Transmission genetics: how genes are transmitted from parents to offspring

It is most easy to understand the results of dihybrid cross if we consider it theoretically as _________________________________________ (Very important to read all)

consisting of two monohybrid crosses conducted separately. Think of the two sets of traits as being inherited independently of each other; that is, the chance of any plant having yellow or green seeds is not at all influenced by the chance that this plant will have round or wrinkled seeds. Thus, because yellow is dominant to green, all F1 plants in the first theoretical cross would have yellow seeds. In the second theoretical cross, all F1 plants would have round seeds because round is dominant to wrinkled. When mendal examined the F1 plants of the dihybrid cross, all were yellow and round, as our theoretical crosses predict. The predicted F2 results of the first cross are 3/4 yellow and 1/4 green. Similarly, the second theoretical cross would yield 3/4 round and 1/4 wrinkled. Figure 3.5 shows that in the dihybrid cross, 12/16 F2 plants are yellow, while 4/16 are green exhibiting the expected 3:1 (3/4:1/4) ratio. Similarly, 12/16 of all F2 plants have round seeds, while 4/16 have wrinkled seeds, again revealing the 3:1 ratio.

Mendal's unit factors represent units of inheritance called _________

genes

During meiosis, however, the chromosome number is not reduced in a random manner. It was apparent to early cytologists that the diploid number of chromosomes is composed of _______________________ pairs. The gametes contain _________________________

homologous pairs one member of each pair, thus the chromosome complement of a gamete is quite specific, and the number of chromosomes in each gamete is equal to the haploid number.

When both alleles are the same (dd or DD) the individual is considered __________ for the trait

homozygous for the trait or a homozygote