Human ChromosomesSection 14.1

In Today’s class….

•We will look at Human chromosome and karyotypes

•Autosomal and Sex chromosomes

•How human traits are transmitted

•How traits can be traced through entire families

• Some genetic disorders which can commonly affect humans

Why are humans are very complicated when it comes to genetics?• Few offspring

• Long life span

•Can not be grown in a lab

•All making piecing together knowledge of human genetics very complicated

Karyotypes

• Human genome – full set of genetic information that a human carries in their DNA

• Chromosomes photographed during mitosis • Chromosomes condensed and easy to view

• A karyotype shows the complete diploid set of chromosomes grouped together in pairs, arranged in order of decreasing size

• Pairs – due to diploid cells – half information from mother, half from father

Sex chromosomes

•Most chromosomes are called autosomal chromosomes or autosomes

• Sex chromosomes are different

•Males : 46,XY, Females: 46,XX

Transmission of human traits

•Human genes follow the same patterns of Mendelian inheritance as the genes of other organisms

•Dominant and Recessive alleles • Many traits follow this pattern• MC1R gene codes for hair and skin color• Blood group Rh factor: simple dominance

•Codominant and multiple alleles • ABO blood group: Codominant • Multiple possibilities

Sex-linked inheritance• X and Y chromosomes determine sex• Genes located on these chromosomes are

referred to as sex linked• Genes on Y chromosome are only found in males

and are passed father to son.• As men only have 1 X chromosome, also possibility

for complications • Humans have 3 genes for color vision, all on x

chromosome• Red-green color blindness affects 1 in 12 males, but 1

in 1 200 females - why the difference?

• Recessive phenotypes of sex linked genetic disorders are much more common in males than females

X-Chromosome inactivation

•One X Chromosome is enough for men,

• In females, the extra X chromosome is often switched off • Forms dense region of nucleus called the Barr

Body

•Common in other mammals• Explains why cats fur coats can exhibit

different characteristics in different parts• Only possible with female cats• If a cats fur has three colors, it is almost

certainly female

Human pedigree

•A pedigree is a chart which shows relationships in a family tree• Shows the presence of absence of a trait• Can be used for any species

•By analyzing a pedigree it is often possible to infer the genotype of family members

•Pedigree analysis allows the application of Mendel’s genetic principles to humans• You can determine if an allele is dominant or recessive, autosomal or sex

linked

Human pedigree example – freckles

Human genetic disordersSection 14.2

How do small changes in DNA molecules affect human traits? •When a gene fails to work, or works improperly, there can be serious

consequences

•There is a direct link between genotype and phenotype

•Changes in a gene’s DNA sequence can change proteins by altering their amino acid sequence, which can directly affect the phenotype of an organisms

•Genetic disorders have a molecular basis

Sickle cell Disease• Caused by defective allele for

beta-globin (a polypeptide in hemoglobin)

• Resultant hemoglobin is less soluble

•When bloods oxygen level decreased, hemoglobin molecules stick together• Clump into long fibers, giving distinctive

sickle like shape

• Sickle cells are more rigid, they get stuck in capillaries

• This can lead to damage to cells, tissues or even organs

Cystic Fibrosis • Most common in Europeans • Most cases result from deletion of just three bases

in the gene for a protein called cystic fibrosis transmembrane conductance regulator (CTFR)

• CTFR normally allows Cl- ions to pass through cell membranes• Without this protein, the cell cannot function properly

• People with one copy of CF allele are unaffected (it is recessive)

• Children with CF have digestive issues, and their lungs and breathing passageways can become blocked with this mucus

Huntington’s disease• Caused by a dominant allele for a protein

found in brain cells• Codon CAG is repeated a lot (more than 40

times)• Unclear why long string of resultant

glutamine causes the disease• Symptoms – mental deterioration, and

uncontrollable movement normally do not appear until middle age• Age disease appears and severity of disease

is related to number of CAG codons

Genetic advantages

• Sickle cell disease and CF are still common amongst humans

•1 in 12 people of African ancestry and 1 in 25 of European ancestry carry the sickle cell gene

•Why hasn’t they both died out?

• Sickle cell gene gives a natural resistance to malaria

•CF allele can help prevent bacterium which cause typhoid – a disease which plagued medieval Europe• People heterozygous for CF had this genetic advantage, but did not have CF

Chromosomal disorders • Sometimes things can go wrong during meiosis • Nondisjunction (means not coming apart) leads to cells

with an abnormal number of chromosomes • Leads to a disorder of chromosome numbers

• Trisomy means three copies of a chromosome• Down syndrome is caused by three copies of chromosome 21

• Turner’s syndrome is when a female only inherits one X chromosome • These women are sterile

• Klinefelter’s syndrome – caused by an extra X chromosome• Again, normally sterile

Studying the human genome

Section 14.3

What techniques are used to study DNA?

• After discovering the importance of DNA, reading it seemed to be impossible

• The smallest chromosome contains nearly 50 million base pairs

• The job was made easier through the use of natural enzymes

• Enzymes can be used to cut, separate and replicate DNA base by base

• Allows scientists to read the base sequences in DNA from any cell

How do you cut DNA?

• Differences in the chemical makeup make DNA relatively easy to separate and extract from other cells and tissues

• Entire DNA molecules are too large – they need to be cut to size

• Many bacteria produce enzymes that do this – restriction enzymes

• Even the largest DNA molecules are cut into precise pieces - restriction fragments

• A few hundred bases in length• Each restriction enzyme cuts DNA at different

sequences of nucleotides

Separating DNA – gel electrophoresis • Gel electrophoresis is used to to

separate and analyze the differently sized fragments

• DNA fragments are placed at one end of a porous gel

• When electric current is applied, DNA Molecules (which are negatively charged) move towards the positive end of the gel

• The smaller the fragment the faster it moves

• End up with DNA bands based on fragment size

• Stains can make these bands visible

Reading the DNA • DNA fragments are placed in test tube with DNA

polymerase alongside the 4 nucleotide bases• Unknown strand is used as a template

• A small number of bases have a chemical dye attached to them

• When these bond replication stops

• End up with a series of color coded fragments of different length

• Separate by gel electrophoresis again

• Order of colored bands tells exact sequence of bases on DNA

• Can be automated by computers – speeding everything up

Human Genome project• A 13 year international effort with the goal of sequencing all 3 billion base

pairs of human DNA, and identifying every human gene

•Other goals included• Sequencing genomes of model organisms to interpret human DNA• Develop technology to support the research• Explore gene functions• Study human variation• Train scientists

• DNA sequencing was basis for human genome project• First DNA was broken into manageable pieces• By determining base sequences in widely separated regions they were able to use

these regions as markers

Sequencing and identifying genes

• Once DNA is marked they used a method called shotgun sequencing• DNA is cut into random fragments• Base sequences are determined• Computer programs analyze this data, and find areas

of overlap • Link fragments by linking overlapping areas

• Reading is not the same as understanding• Scientists look for promoters to identify specific

genes • Sequences that separate introns and exons , and

stop codons also all help in identifying genes

Comparing sequences

•Most of the DNA of unrelated individuals matches base for base with each other

•Only 1 base in 1200 will not match • These are single base differences – Single nucleotide polymorphisms

(SNPs/snips)

• Certain sets of SNPs occur together time and again – haplotypes (haploid genotypes)

• HapMap project started in 2002 to identify these in more detail

Sharing data

•Human genome project was completed in 2003

•Copies of human genome are freely available on the internet

•More data is added on a daily basis

• Lead to a new fields of study:• Bioinformatics – Where IT meets biology • Genomics – study of whole genomes, including genes and their

functions

What we learnt•Only 2 percent of the human genome contains instructions for

synthesizing proteins

•Many chromosomes contain large areas with few genes

•Half the genome is made up of DNA from viruses and other genetic elements

•Project was a great success• Pinpointed genes• Associated particular sequences in genes with numerous diseases and

disorders• 3 millions SNPS identified• Opened up new avenues of research – biotechnology

Issues raised

•Who owns and controls genetic information?

•Who should have access to this information? Insurance companies?

• In 2008 US congress made it illegal to discriminate on the basis of genetic information

•As science progress new laws may follow

What happens next?

•Potential for tailoring treatments for diseases to specific individuals

Does it stop with DNA? • DNA is coiled around protein clusters called

nucleosome to form chromatin • Where chromatin is compact genes are switched

off• Where chromatin opens up gene expression is

enhanced• Process of opening and closing controlled by

enzymes that leave chemical marks, which are affected by stress, diet and disease

• These chemical marks are epigenetic – they are above the level of the genome• They do not affect the base sequence, but affect gene

expression• These marks can be passed onto offspring