Completing and Targeting the Functional Protein

1. Completing and Targeting the Functional Protein • Polypeptide chains • Undergo modifications after the translation process • After translation • Proteins may be modified in ways that affect their three-dimensional shape

2. Proteins • An organism's proteins are the machines that make it work, that make it alive. • Generally speaking, when there's any problem with those proteins, there'll be a problem with the whole organism

3. Protein Folding Protein folding is the process by which a string of amino acids (the chemical building blocks of protein) interacts with itself to form a stable three-dimensional structure during production of the protein within the cell.

4. Folding • Occurs because attractions and repulsions between atoms. Four levels of protein structure: 1°sequence of amino acids in polypeptide chain 2° formed by the hydrogen bonds between amino groups 3° 3-D shape forms-shape due to R-group interaction 4° occurs only if different polypeptide units form

5. Misfolded Proteins • Sent back to the cytoplasm • Tagged • Destroyed • Misfolded proteins not destroyed can cause disease

6. Disorders of Protein Folding • Alzheimer • Lou Gehrig’s • Huntington disease • Parkinson • Cystic Fibrosis • Sickle Cell

7. Cystic Fibrosis • Protein prevented from going to the plasma membrane • Were it controls the flow of chlorine ions • Builds up in the cells • Causes abnormal chloride channels in cells lining the lungs • Buildup of extremely thick mucous Inherited disease –Autosomal recessive -parents are carriers

8. Sickle Cell Disease • Beta globin gene • Valine amino acid replaces glutamic acid • Has aggregated hemoglobin molecules • Causes bending of the RBC • Forming a sickle-shaped Inherited disease –Autosomal recessive -parents are carriers

9. Protein Collagen • Major component of connective tissue • Ehlers-Danlos syndrome • Stretchy skin

10. Alzheimer • One form- autosomal dominant • Protein that monitors storage or use of beta amyloid • Causes increase levels of protein

11. Inheritance • Recessive allele • expression is masked by another • Dominant allele • A gene expressed/even one copy • Autosomal • A chromosome that does not have a gene that determines sex Recessive

12. Autosomal Recessive Inheritance • Affected individuals have a homozygous recessive genotype • Cystic fibrosis (cc) • Heterozygotes – carriers (Cc)

13. Genetics Problem • Man with sickle cell disease • Has unaffected parents • Sister is healthy/husband no family history • Sister wants to know the risk that her children will inherit the allele for sickle cell • What is the probability

14. 1st pedigree • 2nd punnett square • Risk she is a carrier • If she is a carrier what is the chance • Probability – product rule • Calculate the overall risk • Multiply the probability carrier - if so- will pass to child (two events – one depends on the other)

15. Chromosomal Basis of Inheritance Genes reside on chromosomes. Sex Chromosomes and Autosomes Sex chromosomes contain genes that determine an organism’s sex (gender). The remaining chromosomes that are not directly involved in determining the sex of an individual are called autosomes.

16. Karyotypes: Male and Female

17. Chromosomal Inheritance • Sex Determination • In mammals, an individual carrying two X chromosomes is female. • An individual carrying an X and a Y chromosome is male. • Sex chromosomes pair during meiosis I. Meiosis proceeds, paired chromosomes separate = move to different cells. • Sperm has equal chance getting X or a Y chromosome • Egg only gets an X

18. Sex chromosomes • Male mammals, Y chromosome contains a gene called – SRY • Sex-determining Region Y • Codes for protein that causes the gonads of embryo to develop as testes. • Females don’t have SRY gene – develop ovaries

19. Effects of Gene Location • Sex-Linked Genes and Traits • Genes found on the X chromosome are X-linked genes. • A sex-linked trait is a trait whose allele is located on a sex chromosome. • Because males have only one X chromosome, a male who carries a recessive allele on the X chromosome will exhibit the sex-linked trait.

20. XaY XAXA A father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation. (a) Sperm Xa Y XAXa XAY Ova XA XAYa XAY XA (b)  If a carrier mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder. XAXa XAY Sperm XA Y XAXA XAY Ova XA XaY XaYA Xa (c) If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele.  XAXa XaY Sperm Xa Y Ova XAY XA XAXa Xa XaYa XaY Figure 15.10a–c • Sex-linked genes • Follow specific patterns of inheritance

21. Some recessive alleles found on the X chromosome in humans cause certain types of disorders • Color blindness • Duchenne muscular dystrophy • Hemophilia

22. Inheritance of Sex-Linked Genes • Muscular dystrophy • Absence of a key muscle protein – dystrophin • Gene locus on the X chromosome • Hemophilia • Sex-linked recessive disorder • Absence of one or more proteins used for clotting

23. Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders • Large-scale chromosomal alterations • Often lead to spontaneous abortions or cause a variety of developmental disorders • Chromosome Mutations • Chromosome mutations are changes in the structure of a chromosome or the loss or gain of an entire chromosome. • Gene Mutations • Gene mutationsare changes in one or more of the nucleotides in a gene.

24. Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n  1 n + 1 n + 1 n –1 n + 1 n – 1 n n Number of chromosomes (a) (b) Nondisjunction of homologous chromosomes in meiosis I Nondisjunction of sister chromatids in meiosis II Figure 15.12a, b Abnormal Chromosome Number • When nondisjunction occurs • Pairs of homologous chromosomes do not separate normally during meiosis • Gametes contain two copies or no copies of a particular chromosome

25. Alterations of Chromosome Structure • Breakage of a chromosome can lead to four types of changes in chromosome structure • Deletion • Duplication • Inversion • Translocation

26. A F H B C G C D F G B A E H E Deletion (a) A deletion removes a chromosomal segment. C E B C D A C D F G F H B A E H B G Duplication (b) A duplication repeats a segment. B A D A C D E F G H G C B E F H Inversion (c) An inversion reverses a segment within a chromosome. (d) A translocation moves a segment fromone chromosome to another, nonhomologous one. In a reciprocal   translocation, the most common type, nonhomologous chromosomes exchange fragments. Nonreciprocal translocations also occur, in which a chromosome transfers a fragment without receiving a fragment in return. A B M C D G E F G H N O C D E F H Reciprocal translocation M N A O P Q R B P Q R Figure 15.14a–d Alterations of chromosome structure

27. Chromosome structure • Cri-du-chat syndrome • deficiency in segment of the short arm chromosome 5 Missing; with one normal 5

28. Gene location • Linked Genes • Pairs of genes that tend to be inherited together are called linked genes. • Chromosome Mapping • The farther apart two genes are located on a chromosome, the more likely a cross-over will occur. • Researchers use recombinant percentages to construct chromosome maps showing relative gene positions.

29. Gene Technology Copying DNA • DNA identification • 1) isolate • 2) make copies • 3) sort by size, compare (unknown w/known) PCR • Polymerase Chain Reaction Technique used to quickly produce small amounts of DNA fragment Gel Electrophoresis sorts DNA by size (DNA fingerprint)

30. Genetic engineering • Modification of DNA • Change a single nitrogen base • Cut out an entire gene and insert a new one • All modifications of DNA code • The production of rDNA (recombinant DNA) • Pieces of DNA cut and pasted together New DNA are formed, new genes, new proteins

31. Recombinant DNA • Insulin • Growth hormones • Clotting factors • These are techniques of DNA technology used to modify the genome of a living organism • Genome – complete genetic material contained in an individual

32. Human Genome Project • Research effort to sequence all of our DNA • Locate within it all of the functionally important sequences, such as genes. • Applications • Discovery of specific genes responsible for several genetic disorders • Cystic fibrosis • Muscular dystrophy • Colon cancer

33. Genomics • 3 billion letters of the human genetic code have been sequenced • Bioinformatics • Biological science • Computer science • Information technology • BLAST – data base for storage of genes in different organisms

34. Genomics Proteomics • The study of all the proteins • Proteins encode • Carry out the work in the cell Bioinformatics can search DNA sequence/ match specific gene with a protein Microarrays two-dimensional arrangement of DNA/cloned genes show which genes are active in a cell used to classify cancers