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

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

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.

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

Misfolded Proteins

• Sent back to the cytoplasm• Tagged• Destroyed• Misfolded proteins not destroyed can cause

disease

Disorders of Protein Folding

• Alzheimer • Lou Gehrig’s• Huntington disease• Parkinson• Cystic Fibrosis• Sickle Cell

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

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

Protein Collagen

• Major component of connective tissue– Ehlers-Danlos syndrome

• Stretchy skin

Alzheimer

• One form- autosomal dominant• Protein that monitors storage or use of beta

amyloid• Causes increase levels of protein

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

Autosomal Recessive Inheritance

• Affected individuals have a homozygous recessive genotype

• Cystic fibrosis (cc)• Heterozygotes – carriers (Cc)

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

• 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)

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.

Karyotypes: Male and Female

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

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

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.

• 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

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

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

• 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

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)

Alterations of Chromosome Structure

• Breakage of a chromosome can lead to four types of changes in chromosome structure– Deletion– Duplication– Inversion– Translocation

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.

Chromosome structure

• Cri-du-chat syndrome– deficiency in segment of the short arm

chromosome 5 Missing; with one normal 5

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.

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)

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

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

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

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

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