Allelic variation

Genetics PPT with MCQ discussion

1. Anubha kumari Assistant professor Department of biotechnology Annada college Hazaribagh jharkhand ALLELIC VARIATION

2. Genes are segments of DNA that code for a particular trait . Traits  are physical characteristics that we see in each other. They include characteristics such as eye color, hair color, height, weight, skin tone, etc. Now let's focus on those traits for a minute. There are many different eye colors, hair colors, and other physical attributes. That's because there is more than one version of a particular trait, such as blue eyes and brown eyes.  Alleles  are those different versions of a trait. So while everyone has the gene for eye color, people may possess different alleles (or versions) of that gene.

3. Alleles and Physical Appearance Alleles come in all shapes and sizes. One of the more common ways to introduce people to genetics is with the concepts of  dominant  and  recessive  alleles. Dominant alleles show up in the physical appearance of organisms. Recessive alleles are hidden or masked by the dominant allele. They only show up where there isn't a dominant allele present. All people have two alleles for every gene (one from each parent). For example, take a look at human ear lobes. The allele for unattached ear lobes is dominant to the allele for attached ear lobes. Therefore, if someone has unattached ear lobes, they possess at least one dominant allele. If they have attached ear lobes, they possess two recessive alleles.

4. Allelic variation An allele (short for allelomorph ) is a variant of a gene were the DNA sequence differs between two or more variants. Allelic variation describes the presence or number of different allele forms at a particular locus (locus or loci = place) on a chromosome (allelic variation is sometimes used more loosely to describe the overall diversity present).

5. During domestication(GM) the number of alleles that are fixed within a crop type is greatly reduced compared to the variation that is left behind in the genepool ( The total number of genes of every individual in an interbreeding population). Therefore there may be many unadapted useful allelic variants that could be used to improve our domesticated crop types.

6. Unattached and Attached Ear Lobes It's important to remember that the concepts of dominant and recessive alleles are useful for understanding basic genetics. While humans have approximately 20,000-25,000 genes, most of them do not fall into the dominant or recessive categories. As discussed earlier, alleles are versions of a gene, and there are many ways these can be expressed.

7. A third kind of allele is the  co-dominant  allele. Co-dominance is when both versions of the allele present in the organism. Since genetics are more personable when we look at ourselves, let's use human blood type as our example. Human blood group can generally be categorized using three letters: A, B, and O. These letters represent your alleles (versions) of the blood type trait. In this case, both the A and B alleles are dominant; O is recessive.

8. everyone has two alleles, so, if a person were to receive an 'A' allele from mom and a 'B' allele from dad, that person would be blood type 'AB.' If that same person had instead received an 'A' from mom and an 'O' from dad, that person would be blood type 'A', since A is dominant to O.

9. MUTIPLE ALLELES Alleles are alternative forms of a gene, and they are responsible for differences in phenotypic expression of a given trait (e.g., brown eyes versus green eyes). A gene for which at least two alleles exist is said to be polymorphic. Instances in which a particular gene may exist in three or more allelic forms are known as multiple allele conditions. It is important to note that while multiple alleles occur and are maintained within a population, any individual possesses only two such alleles ( a equivalent   loci  on  homologous chromosomes ).

10. For example, at the gene locus for the ABO blood type  carbohydrate antigens  in humans,classical genetics recognizes three alleles, I A , I B , and i, that determine compatibility of blood transfusions. Any individual has one of six possible genotypes(I A I A , I A i , I B I B , I B i , I A I B , and ii) that produce one of four possible phenotypes: "Type A" (produced by I A I A  homozygous and I A i heterozygous genotypes), "Type B" (produced by I B I B  homozygous and I B i heterozygous genotypes), "Type AB" produced by I A I B  heterozygous genotype, and "Type O" produced by ii homozygous genotype.

11. Allelic dominance in genetic disorders A number of  genetic disorders  are caused when an individual inherits two recessive alleles for a single-gene trait. Recessive genetic disorders include  albinism (  no melanin production .),   cystic fibrosis ( damages the lungs and digestive system .),   galactosemia ( affects an individual's ability to metabolize the sugar galactose properly),   phenylketonuria  (PKU), and  Tay –Sachs disease ( destroys nerve cells in the brain and spinal cord).

12. Other disorders are also due to recessive alleles, but because the gene locus is located on the X chromosome, so that males have only one copy (that is, they are  hemozygous ), they are more frequent in males than in females. Examples include red-green  color blindness  and  fragile X syndrome (intellectual disability). Other disorders, such as  Huntington disease (nerve cells in the brain break down over time.), occur when an individual inherits only one dominant allele.

13. Epialleles While  heritable traits  are typically studied in terms of genetic alleles,  epigenetic  marks such as  DNA methylation  can be inherited at specific genomic regions in certain species, a process termed  transgenerational epigenetic inheritance . The term  epiallele  is used to distinguish these heritable marks from traditional alleles, which are defined by  nucleotide sequence .  A specific class of epiallele , the  metastable epialleles , has been discovered in mice and in humans which is characterized by stochastic (probabilistic) establishment of epigenetic state that can be mitotically inherited

14. GENE FUNCTION The chromosomes within our cells contain an enormous amount of information. It is estimated that humans have somewhere around 30,000 genes. Each gene codes for an RNA molecule that is either used directly or used as a guide for the formation of a protein such as the insulin shown earlier. Information in our cells generally flows in a predictable order from the storage form of the information (DNA) through the working form (RNA) into the final product (protein).

15. Transcription The goal of transcription is to make an RNA copy of a gene. This RNA can direct the formation of a protein or be used directly in the cell. All cells with a nucleus contain the same exact genetic information. As discussed, only a small percentage of the genes are actually being used to make RNA at any given time in a particular cell. The transcription process is very tightly regulated in normal cells. Genes must be transcribed at the correct time. The RNA produced from a gene must be made in the correct amount. ONLY the required genes should to be transcribed. Turning transcription off is just as important as turning it on.

16. Assembly A classical view of PIC formation at the promoter involves the following steps: TATA binding protein  ( TBP , a subunit of TFIID) binds the  promoter , creating a sharp bend in the promoter DNA. TBP-TFIIA interactions recruit TFIIA to the promoter. TBP-TFIIB interactions recruit TFIIB to the promoter. TFIIB-RNA polymerase II and TFIIB-TFIIF interactions recruit RNA polymerase II and TFIIF to the promoter. TFIIE joins the growing complex and recruits TFIIH which has protein kinase activity(phosphorylates RNA polymerase II within the CTD)and DNA helicase activity(unwinds DNA at promoter). It also recruits nucleotide-excision repair proteins .

17. Subunits within TFIIH that have  ATPase  and  helicase  activity create negative  superhelical  tension in the DNA. Negative superhelical tension causes approximately one turn of DNA to  unwind  and form the  transcription bubble . The template strand of the transcription bubble engages with the RNA polymerase II active site. RNA synthesis begins. After synthesis of ~10 nucleotides of RNA, and an obligatory phase of several abortive transcription cycles, RNA polymerase II escapes the promoter region to transcribe the remainder of the gene.

18. Initiation Getting started: Initiation In  initiation , the ribosome assembles around the mRNA to be read and the first tRNA (carrying the amino acid methionine, which matches the start codon, AUG). This setup, called the initiation complex, is needed in order for translation to get started.

19. Elongation Elongation  is the stage where the amino acid chain gets  long er. In elongation, the mRNA is read one codon at a time, and the amino acid matching each codon is added to a growing protein chain. Each time a new codon is exposed: A matching tRNA binds to the codon The existing amino acid chain (polypeptide) is linked onto the amino acid of the tRNA via a chemical reaction The mRNA is shifted one codon over in the ribosome, exposing a new codon for reading

20. During elongation, tRNAs move through the A, P, and E sites of the ribosome, as shown above. This process repeats many times as new codons are read and new amino acids are added to the chain.

21. Finishing up: Termination Termination  is the stage in which the finished polypeptide chain is released. It begins when a stop codon (UAG, UAA, or UGA) enters the ribosome, triggering a series of events that separate the chain from its tRNA and allow it to drift out of the ribosome. After termination, the polypeptide may still need to fold into the right 3D shape, undergo processing (such as the removal of amino acids), get shipped to the  right place in the cell , or combine with other polypeptides before it can do its job as a functional protein.

22. Transcription Factors  Some examples of transcription factors that malfunction in human cancers are: p53  - The gene that codes for the p53 transcription factor (protein) is mutated in over half of all cancers of any type. The protein that the  p53  gene codes for is important because it controls the transcription of genes that are involved in causing cells to divide .   p53  gene are   tumor suppressors .

23. Rb  - The protein product of this gene is a transcription factor with an interesting function. It actually works by  blocking  other transcription factors. In this way,  Rb  prevents transcription of key genes required for cell division to progress. Initially described as a gene mutated in retinoblastoma, a cancer of the eye from which the gene derives its name, the Rb protein is now known to play a role in many different cancer types.   Rb  gene are  tumor suppressors .

24. The estrogen receptor (ER) - This protein binds to estrogen that enters the cell. Estrogen is a steroid (lipid) hormone produced by the ovaries. The combination of protein and hormone then acts as a transcription factor to turn on genes that enable the target cells to divide. The receptor is active in the cells of the female reproductive organs, such as breasts and ovaries. Because of this, estrogen is recognized as a factor that enhances the growth of certain cancers arising in these tissues.

25. Translation After the messenger RNA (mRNA) is produced through the transcription process just described, the mRNA is processed in the nucleus and then released into the cytosol. The mRNA is then recognized by the ribosomal subunits present in the cytosol and the message is 'read' by the ribosome to produce a protein. The information for the direction of protein formation is encoded in the sequence of nucleotides that make up the mRNA. Groups of three nucleotides (called codons) are 'read' by the ribosome and lead to the addition of a particular amino acid into the growing polypeptide (protein).

26. Gene Function Summary The Central Dogma The DNA in our chromosomes contains genes that get transcribed into RNA. There are several different types of RNA ( tRNA , mRNA, rRNA , etc.). They are composed of the same building blocks but have different functions, locations and structures. Messenger RNA (mRNA) may be translated into a protein. The standard information flow is: DNA→RNA→Protein The set of genes that are 'on' at any given time is critical. Different genes need to be 'on' at different times depending on the needs and functions of any particular cell .

27. Transcription The goal of transcription is to make an RNA copy of a gene. Transcription factors bind to the starting point of genes in order to identify the spot where transcription begins. p53 ,  Rb , the estrogen receptor are all transcription factors that malfunction in cancers. The process of transcription is divided into several distinct steps: Transcription factor recognizes and binds to a gene's start site (promoter). An RNA-making enzyme (RNA polymerase) binds to the transcription factor. The enzyme makes an RNA copy of the gene. The enzyme falls off and the RNA is released. The RNA will either remain in the nucleus or it will exit into the cytosol.

28. Translation The goal of translation is to make a protein using the information encoded in mRNA. The process of translation is divided into several steps: mRNA leaves the nucleus and is recognized and bound by ribosomal subunits in the cytosol. The ribosome 'reads' the RNA three nucleotides (one codon) at a time. The ribosome inserts the amino acid corresponding to the codon into the growing protein. The ribosome encounters a stop codon and terminates protein synthesis. The protein enters a highly regulated folding process and obtains a fully folded structure. Genes that control the proper folding, transportation, activity and eventual destruction of proteins are often damaged or malfunctioning in cancer.

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39. ANSWERS 1. B 2. D 3. C 4. C 5. A 6. B 7. A 8. A 9. D 10. B