Completing and Targeting the Functional Protein
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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
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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
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Protein FoldingProtein 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.
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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 groups3° 3-D shape forms-shape due to R-group
interaction4° occurs only if different polypeptide units form
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Misfolded Proteins
• Sent back to the cytoplasm• Tagged• Destroyed• Misfolded proteins not destroyed can cause
disease
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Disorders of Protein Folding
• Alzheimer • Lou Gehrig’s• Huntington disease• Parkinson• Cystic Fibrosis• Sickle Cell
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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 mucousInherited disease –Autosomal recessive
-parents are carriers
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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
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Protein Collagen
• Major component of connective tissue– Ehlers-Danlos syndrome
• Stretchy skin
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Alzheimer
• One form- autosomal dominant• Protein that monitors storage or use of beta
amyloid• Causes increase levels of protein
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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 sexRecessive
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Autosomal Recessive Inheritance
• Affected individuals have a homozygous recessive genotype
• Cystic fibrosis (cc)• Heterozygotes – carriers (Cc)
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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
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• 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)
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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.
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Karyotypes: Male and Female
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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
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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
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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.
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• Sex-linked genes– Follow specific patterns of inheritance
Figure 15.10a–c
XAXA XaY
Xa Y
XAXa XAY
XAYXAYa
XA
XA
Ova
Sperm
XAXa XAY
Ova XA
Xa
XAXA XAY
XaYXaYA
XA YSperm
XAXa XaY
Ova
Xa Y
XAXa XAY
XaYXaYa
XA
Xa
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.
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.
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.
(a)
(b)
(c)
Sperm
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• Some recessive alleles found on the X chromosome in humans cause certain types of disorders– Color blindness– Duchenne muscular dystrophy– Hemophilia
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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
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• 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 mutations are changes in one or more of the
nucleotides in a gene.
Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders
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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
Figure 15.12a, b
Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
Gametes
n + 1n + 1 n 1 n – 1 n + 1 n –1 n nNumber of chromosomes
Nondisjunction of homologouschromosomes in meiosis I
Nondisjunction of sisterchromatids in meiosis II
(a) (b)
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Alterations of Chromosome Structure
• Breakage of a chromosome can lead to four types of changes in chromosome structure– Deletion– Duplication– Inversion– Translocation
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Alterations of chromosome structure
Figure 15.14a–d
A B C D E F G HDeletion
A B C E G HF
A B C D E F G HDuplication
A B C B D EC F G H
A
A
M N O P Q R
B C D E F G H
B C D E F G HInversion
Reciprocaltranslocation
A B P Q R
M N O C D E F G H
A D C B E F HG
(a) A deletion removes a chromosomal segment.
(b) A duplication repeats a segment.
(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 exchangefragments. Nonreciprocal translocationsalso occur, in which a chromosome transfers a fragment without receiving afragment in return.
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Chromosome structure
• Cri-du-chat syndrome– deficiency in segment of the short arm
chromosome 5 Missing; with one normal 5
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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.
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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)
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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
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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
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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
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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
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GenomicsProteomics• The study of all the proteins
– Proteins encode • Carry out the work in the cellBioinformatics can search DNA sequence/ match specific gene with
a proteinMicroarrays
two-dimensional arrangement of DNA/cloned genesshow which genes are active in a cellused to classify cancers