Old terms in a new language – 第 2 页

Mendel’s Genetics [4]: examples of mutiple alleles

All the examples used in last classes have employed genes with only two alternative alleles. But the majority of genes exist in several different forms, multiple alleles. This is caused by the mutations of bases at different sites within the same gene, thus affecting different amino acids in the encoded protein.

examples of multiple-allele traits/diseases:

the human β-globin gene where a specific mutation at one site of the gene results in an allele responsible for the hereditary syndrome sickle cell (picture)anaemia, while mutations at several other sited sites in the gene cause a different syndrome, β-thalassemia(beta地中海贫血),
A SICKLE CELL,image from the Internet

Beta-thalassemia, inherited blood disorder caused by reduced or absent synthesis of the beta chains of hemoglobin, resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals.

Although they are alterations of the same gene, the changes are to different codons(a specific sequence of three consecutive nucleotides that is part of the genetic code and that specifies a particular amino acid in a protein or starts or stops protein synthesis). The resulting proteins have variant beta-globins with discrete differences in amino acid sequence and so behave differently.

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In rabbits, multiple alleles of one gene are responsible for a number of different coat color phenotypes.

Here we go, a little confusing but, interesting:

There are four members of the allelic series: agouti, chinchilla, Himalayan and albino. When homozygous, each series produces a distinct coat pattern. When heterozygous, there is a clear pattern of dominance. Agouti is dominant over all the alleles, chinchilla is dominant over Himalayan and albino, while Himalayan is dominant over albino, which fails to produce any pigment and hence is recessive to the others…Hope your mind is still clear!

1, Agouti rabbit: the wild rabbit.

genetics 4 an agouti rabbit — AN AGOUTI RABBIT, image form the Internet

If you blow into the fur of an Agouti rabbit, you will see “bandings” of different colors along the shaft of the hair, being blue, black, tan, fawn. The Agouti also has light tan coloring around the nostrils and at the back of the neck. The belly is cream.(http://rabbit.wikia.com/wiki/Agouti)

2, Chinchilla rabbit: soft, grey fur.

genetics 4 A five-week-old Chinchilla rabbit — A FIVE-WEEK-OLD CHINCHILLA RABBIT, image from the Internet

Chinchilla Rabbits originated in France and were bred to standard by M. J. Dybowski. They were introduced to the United States in 1919. (wikipedia)

3. Himalayan rabbit: white body with colored points, recognized colors are black, blue, chocolate and lilac.

A HIMALAYAN RABBIT, image from the Internet

red eyes; posed stretched out, body to be 3.5 head lengths. They are the ancestors of Californians, one of the most common meat rabbits.(wikipedia: Himalayan_rabbit)

4. Albino rabbit: completely white since it’s missing the melanin which determines the color of their skin, eyes, and fur.

genetics 4 albino rabbits — AN ALBINO RABBIT, image from the Internet

Not all white rabbits are albinos, so you’ll need to check their eyes. If their eyes are red or pink and their hair is totally white, they would be considered an albino. They are not rare.

An albino rabbit may not have the greatest eyesight due to their lack of eye pigment. Since their eyesight is not the best, they should be caged or kept inside since they may not be able to see predators.(http://www.ask.com/question/albino-rabbits)

Having seen so much about rabbits, hope you haven’t forgotten what we were doing before those cute bunnies. We were learning about examples of multiple alleles of one gene.

the human ABO blood group system.

(all form wikipedia: ABO blood group system:)

The ABO blood type is controlled by a single gene (the ABO gene) with three types of alleles inferred from classical genetics: i, I^A, and I^B. The gene encodes a glycosyltransferase— an enzyme that modifies the carbohydrate content of the red blood cell antigens.

The I^A allele gives type A, I^B gives type B, and i gives type O.

Both I^A and I^B are dominant over i, so only ii people have type O blood. Individuals with I^AI^A or I^Ai have type A blood, and individuals with I^BI^B or I^Bi have type B.

I^AI^B people have both phenotypes, because A and B express a special dominance relationship: codominance(we talked about it last class), which means that type A and B parents can have an AB child.

A type A and a type B couple can also have a type O child if they are both heterozygous (I^Bi,I^Ai)

Hope your mind is still clear!

NOTE: the concept of multiple alleles of one gene is totally different from multiple-gene inheritance.

A polygene, multiple factor, multiple gene inheritance, or quantitative gene is a group of, non-allelic, genes that together influence a phenotypic trait.

the blueprint of life [2]: primary and secondary structure of DNA

Molecular structure of DNA:

professor Dong first showed us where DNA is:

Then he introduced the molecular structure of DNA with 4 parts:

1. Primary structure of DNA:

Arrangement of nucleotides along a DNA chain.

Annie: So…the primary structure of DNA is a line.

Conventionally, the repeating monomers of DNA are represented by their single letters A, T, G, C.

Professor: There’s a convention to write the DNA sequence with 5′ at the left, that is, in a 5′ to 3′ orientation from left to right.

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2. Secondary structure of DNA—stabilized partial structure formed by polymers of nucleotide

Professor Dong: First, please familiarize yourselves with Chargaff’s Rule:

A+G=T+C & G+T=A+C

↓↓

A=T & G=C

(Chargaff’s Rule)

(Based on analysis of the chemical composition of duplex DNA in the early 1950s, E. Chargaff deduced these rules about the amounts of different nucleotides in DNA.)

Professor: The secondary structure of DNA is a partial structure formed by polymers of nucleotide. The structure is referred to as the double-helix structure.

Two separate chains of DNA are wound around each other, each following a helical (coiling) path, resulting in a right-handed double helix structure.

In 1953, Watson and Click proposed the DNA double-helix structure based on Chargaff’s Rule and DNA Crystallography and X-ray diffraction images of DNA structure by Wilkins and Franklin. (Rosalind Franklin, who was not that well-known as Watson, Click and Wilkins but apparently played a equally significant role in the discovery of the structure.The whole was later nominated Nobel Prize but her, is that even fair?)

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The backbone of duplex DNA is a serious of phosphodiester group (the covalent linkage of a phosphate group between the 5′-hydroxyl of one sugar and the 3′-hydroxyl of the next, that is , repeats of P-sugar unit) linked by phosphodiester bond.

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The strands are joined noncovalently by hydrogen bonding between the bases on opposite strands, to form base pairs.

There are around 10 base pairs per turn in the DNA double-helix. The two strands are oriented in opposite directions in terms of their 5’to3′ direction(the nucleotides in one strand is opposite to their direction in the other strand).

More crucially, the two strands are complementary in terms of sequence. The bases hydrogen-bond to each other as purine-pyrimidine pairs which have very similar geometry and dimensions.

A–T: 2 H-bonds ; C–G: 3 H-bonds

5’- A T G T C -3’

¦¦ ¦¦ ¦¦¦ ¦¦ ¦¦¦

3’- T A C A G -5’

Thus, the sequence of one strand uniquely specifies the sequence of the other, with all that which implies for the mechanism of replication of DNA and its transcription to RNA.

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Professor Dong added:

Between the backbone stands run the major and minor grooves.

In a detailed analysis of DNA structure, there are two types of grooves that can be seen; the major groove has the nitrogen and oxygen atoms of the base pairs pointing inward toward the helical axis, while in the minor groove,the nitrogen and oxygen atoms point outwards;

Shown by prof.Dong, MAJOR GROOVE A-T

Shown by prof.Dong, MAJOR GROOVE G-C

Major Groove Minor Groove

Depth: 8.5 Å Depth: 7.5 Å

Width: 11.7 Å Width: 5.7 Å

Å

Definition: Symbol for Ångström, a unit equal to 0.1 nanometer, mainly used in expressing sizes of atoms, lengths of chemical bonds, and wavelengths of electromagnetic radiation.

Supplement: The unit is named after the Swedish physicist, Ångström, Anders Jonas.

picture from Instant Notes in Molecular Biology

Professor: The major groove is more dependent on base composition. and major grooves and minor grooves are also recognition and binding sites for certain protein factors, and are involved in the regulation of gene expression.

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Professor: Summary of “Double Helix” Model (B-DNA):

Right Handed Double Helix

Outside: P-Sugar backbone

Inside: Base pairing linked by H-bonds

Minor and Major grooves

（note: bp=base pair(s)）

the blueprint of life[1]

Of course the blueprint of life is DNA.

DNA is important because it is the genetic material ←contain all the info for the synthesis and functioning of a living form duplicate and passes through to the next generation.

Hearing this Annie questioned herself: DNA is not the genetic for ALL viruses. RNA “blueprints” for the rest of the viruses. Virus, though not even having a cell structure, is a form of life. So why not be fair, and say the blueprint of life are DNA and RNA?

Professor Dong continued,

Proofs:

Bacterial Transformation Experiment

—Griffith, 1928

Professor: So what is the transforming principle?

Annie: It could be a cool type of enzyme that moved the toxic part of S strain onto R strain…

Professor: Well, Enzyme did help a lot in the experiment we’ll talk about later, but it is not the hero of the story.

Annie: So what’s the story?

Professor:

—Avery et al., 1944

slide shown by Prof. Dong ,AVERY REPEATED GRIFFITH’S EXPERIMENT WITH MODIFICATION

Only DNA is responsible for the transformation.

Annie thought: Well, there still existed possibilities that DNA and some other things that were not sugar, lipid or protein cooperated to complete the transformation… The “other things” also contributed to the transformation but could not complete it without DNA? In this case DNA is not the only one that is responsible,

T2 Bacteriophage Infection (Blender Experiment)

—Hershey &Chase, 1952

Experiment 1

Experiment 2

Radioactive labeling of proteins and DNA

The professor continued. So now let’s go deeper and see the chemical composition of DNA.

A 5-carbon sugar , hand in hand with base group and phosphorous group, thought Annie.

It’s not that simple as you learned in high school, said the professor. We need to know the chemical composition of the base group, deoxyribon and phosphorous group as well.

sugar group — slide shown by Prof. Dong,SUGAR GROUP

Professor:

Base — slide shown by Prof. Dong,BASE GROUPS

Annie thought: Pyrimid-ine, Could it have anything to do with the Pyramid in Egypt?

The professor was explaining the structure and Annie didn’t interrupt him with her question.

After class, Annie searched the Internet for an answer, and this is what she found.

The professor continued.

Bonds

P group——phosphester bond–—Sugar—–glycosidic bond—–B group

Mendel’s Genetics[2]: The monohybrid cross

Keywords:

Phenotype

Any character (trait) which can be shown to be inherited, such as eye color, leaf shape or an inherited disease, such a cystic fibrosis, is referred to as a phenotype.

Description: A fly may be described as having a red-eyed phenotype. A child may be described as displaying the cystic fibrosis phenotype.

Genotype

The pattern of genes that are responsible for a particular phenotype in a individual is referred to as genotype.

Dominance

In hybrids between two individuals displaying different phenotypes, only one phenotype may be observed. This phenotype is referred to as the dominant trait and the un-shown one the recessive.

For instance, if the wife has wide eyes while the husband has small eyes, and their little girl has wide eyes, then the wide eyes are dominant to small eyes.

Pure-breeding lines

Organisms which have been inbred for many generations in which a certain phenotype remain the same.Pedigree breeds of dogs or cats are commonplace examples of pure-breeding lines.

A puppy from two purebred dogs of the same breed, for example, will exhibit the traits of its parents, and not the traits of all breeds in the subject breed’s ancestry.

Homozygous: Individuals with two identical copies of a gene.

“True breeding (pure-breedind) organisms are always homozygous for the traits that are to be held constant.”

Heterozygous: Individuals with two different copies of the gene.
Alleles: The different variants of a gene.

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Mendel made a cross between two pure-breeding lines of pea plants, one of which had violet petals and the other white petals. The hybrids produced in this cross were referred to as the F1 (first filial) generation.

In Mendel’s experiment, the ratio of violet pedals and white ones in the second filial were very close to 3 to 1, which applied to the theoretic reasoning shown above.

He did many other experiments focusing on different types of genotypes of the pea plants and the results were shockingly similar. The hidden phenotype in the first filial reappeared in the second filial and the ratio of the dominant to the recessive phenotype were all close to 3 to 1.

The 3:1 ratio is referred to as the monohybrid ratio and is the basis for all patterns of inheritance in higher organisms.

One simple extension of the 3:1 phenotype ratio is a 1:1 ratio, produced when a heterozygous F1 individual is crossed to the homozygous-recessive parent. The process is known as testcross.

Testcross is useful in any condition when it is necessary to determine whether an individual is heterozygous or homozygous. Conceivable that if F2 all have dominant phenotype, then the tested parent is homozygous-dominant; if F2 have a 1:1 ratio of dominant and recessive phenotype, then the tested parent is heterozygous.

Review of Mendel’s Genetics

Here I found a great page story-telling Mendel’s Genetics.Can’t be more suitable as a revision of what we learned about genetics and inheritance in high school. >>Mendel’s Genetics

I believe by reading the link page you have remembered the principles of Mendel’s Genetics. We’ll summarize these principles again in next posts.

While Mendel’s research was with plants, the basic underlying principles of heredity that he discovered also apply to people and other animals because the mechanisms of heredity are essentially the same for all complex life forms.”

It must be a cliche to summarize the success factors of Mendel’s experiments, but it has to be done, for many of the factors are still important for today’s experimentalists.

Firstly, before the experiment,Mendel spent a long time observing different traits of the peas and decided which traits he was going to focus on in the after experiments. He was prepared, had anticipation and, perhaps already held some hypothesis of what was going to happen.

Then it was the choice of his “lab-rats”. As the link page says,”Mendel picked common garden pea plants for the focus of his research because they can be grown easily in large numbers and their reproduction can be manipulated. ” Based on a large number of offspring, the resulting statistics can be assumed as very close to theoretic statistics. In this case, it’s way more convenient to study the traits of these peas than those of some fragile and rare pole plants.

More important, “pea plants have both male and female reproductive organs. As a result, they can either self-pollinate themselves or cross-pollinate with another plant. In his experiments, Mendel was able to selectively cross-pollinate purebred plants with particular traits and observe the outcome over many generations. This was the basis for his conclusions about the nature of genetic inheritance.”

Reproductive
structures of
flowers

drawing of a flower cross-section showing both male and female sexual structures — the picture is from http://anthro.palomar.edu

Last but not least, Mendel was a pioneer in applying Math(Statistics) to experiment analysis. He rounded the ratio of numbers of different traits to a whole number and discovered the astonishing similarity of all the results.

In high school that’s all the factors, but actually there’s more. For one, Mendel succeeded because all the genes that controlled traits he picked to observe happened to be on different chromosomes. Otherwise, the phenomena of “linkage” would have appeared (which we’ll talk about later)and he should never have had such a groundbreaking discovery.

What is molecular biology

Generally speaking, molecular biology is the study of structure and function of macromolecules such as nucleic acids, proteins and other polymers. In a narrow sense, molecular biology focuses on nucleic acids and their activities, such as transcription, translation, DNA replication, recombination, translocation and so on.

Writing in Nature in 1961, William Astbury described molecular biology as:

“…not so much a technique as an approach, an approach from the viewpoint of the so-called basic sciences with the leading idea of searching below the large-scale manifestations of classical biology for the corresponding molecular plan. It is concerned particularly with the forms of biological molecules and […] is predominantly three-dimensional and structural—which does not mean, however, that it is merely a refinement of morphology. It must at the same time inquire into genesis and function.”

Foundation of Molecular Biology:

1869: Discovery of nucleic acids (nuclein)
F. Miescher
1944: Proofing of nucleic acids are genetic materials
1953: Proposition of DNA structure – “double helix model” (Watson and Crick, 1962 Nobel)
1954: Establishment of “central dogma” (Crick)
1958: Mechanism of DNA replication (Meselson and Stahl)
1961: “Operon” model of gene regulation (Jacob and Monod)
1964: Identification of genetic codes (Nirenberg, 1968 Nobel)

Era of Genetic Engineering

1970: Discovery of reverse transcriptase (Temin and Baltimore, 1975 Nobel)
1972: First recombinant DNA in vitro (Berg, 1980 Nobel)
1973: First transformation of hybrid plasmid into E. coli (Cohen and Boyer)
1977: First genetically modified product (Boyer, somatostatin )
1977: DNA sequencing methods (Sanger and Gilbert, 1980 Nobel)
1985: DNA in vitro amplification technology-PCR）
1970: Discovery of reverse transcriptase (Temin and Baltimore, 1975 Nobel)
1972: First recombinant DNA in vitro (Berg, 1980 Nobel)
1973: First transformation of hybrid plasmid into E. coli (Cohen and Boyer)
1977: First genetically modified product (Boyer, somatostatin)
1977: DNA sequencing methods (Sanger and Gilbert, 1980 Nobel）
1985: DNA in vitro amplification technology-PCR（Mullis, 1993 Nobel)

Era of Genomics and post-Genomics

1986: Establishment of “Genomics” concept (Dulbecco, Roderick and McKusick)
1990: Human genome project starts (USA department of energy)
2003: Completion of sequence mapping of human genome (International HGP organization)
2003-now: functional analysis of genome (post-genomics)

Genome Projects-Current Researches:

Genetic engineering

GMO (Genetically modified organism 基因修饰生物)
Cancer and gene therapy

Regulation analysis of gene expression

Signal transduction, TFs, RNA splicing, etc

Structural and functional analysis of biological macromolecules

X-ray crystallography, NMR, EM etc
Yeast two-hybrid, immunoprecipitation etc

Genomics, proteomics and bioinformatics
…..

Hotspots