Chapter 12: Human GeneticsChapter 12: Human Genetics

Human Genome Project

• identify all the approximately 20,000-25,000 genes in human DNA • determine the sequences of the 3 billion chemical base pairs that make up human DNA • store this information in databases • improve tools for data analysis • transfer related technologies to the private sector • address the ethical, legal, and social issues (ELSI) that may arise from the project.

Though the HGP is finished, analyses of the data will continue for many years.

Chromosome Map (used to identify inheritance patterns)• Diagram showing the RELATIVE LOCATIONS of genes on a chromosome.

Comparing genomesComparing genomes On the left - human chromosome number 2 On the left - human chromosome number 2

(of 23). (of 23). On the right -matching chromosomes from On the right -matching chromosomes from

a chimpanzee. a chimpanzee. If you compare carefully, you will see that If you compare carefully, you will see that

the details line up. However, something the details line up. However, something has happened: a has happened: a translocationtranslocation mutation has mutation has changed the number of chromosomes. changed the number of chromosomes.

The two species have a common ancestor. The two species have a common ancestor. Since chimpanzees, gorillas, orangutans, Since chimpanzees, gorillas, orangutans, and bonobos all have 24 chromosome and bonobos all have 24 chromosome pairs, it is assumed that the common pairs, it is assumed that the common ancestor had 24 pairs. Since the time of ancestor had 24 pairs. Since the time of that ancestor, humans had a fusion that ancestor, humans had a fusion mutation that turned 24 into 23. mutation that turned 24 into 23.

Other major visible difference -there are 9 Other major visible difference -there are 9 inversionsinversions between man and chimp. between man and chimp.

Mutation (abnormal BASE sequence)• A change in the DNA that can involve an ENTIRE CHROMOSOME or just a SINGLE NUCLEOTIDE;(NOTE: mutations can occur in ALL cell types).

(1) Germ-cell (i.e., Sex cell) Mutations• Can be INHERITED from parent to offspring (i.e., Occur in the SEX cells (gametes) of an organism)

(2) Somatic Mutations (body cell mutations)• NON-sex cell and can AFFECT the organism; Types of CANCER result from SOMATIC mutations.

(3) Lethal Mutations (lead to cell death)• GENES result in major DEVELOPMENTAL flaws typically BEFORE birth.

Chromosome MutationsChromosome Mutations (large-scale change)• Changes in the STRUCTURE of the chromosome or the LOSS or ADDITION of an ENTIRE chromosome.

Deletion Inversion

Translocation

Nondisjunction Nondisjunction (results in Monosomy or Trisomy)

• Chromosomes FAIL to separate during meiosis, resulting in one gamete with an EXTRA chromosome and one gamete, SHORT a chromosome.

Turner’s Syndrome - Monosomy X

Down Syndrome (a.k.a., Trisomy-21)

Patau Syndrome (trisomy 13) Kleinfelter’s - XXY

(B) Gene Mutation (smaller-scale change)

• A SINGLE base within a TRIPLET becomes CHANGED (Point Mutations, Substitutions, Insertions, Deletions)

(1) Point Mutation (i.e., mutation occurs at a SINGLE POINT-3 types)• A substitution, insertion, or deletion of a SINGLE BASE in a sequence.(2) Substitutions (do NOT cause a FRAMESHIFT)• One base is REPLACED with a DIFFERENT base, resulting in a DIFFERENT codon (possibly a DIFFERENT amino acid).

(3) Sickle-Cell Anemia (inherited disease)• Caused by a SUBSTITUTION of an adenine (A) for a thymine (T) in a DNA sequence (results in DEFECTIVE hemoglobin).

Frameshift Mutation (deletion AND insertion mutations ONLY)

• The deletion or insertion of a SINGLE base causes the REMAINING codons to be REGROUPED, (incorrectly)…consider the following sequence:

THE DOG AND THE BAT CAN EAT THE RAT

Knock out the “H” in the first codon (deletion) and the entire frame will SHIFT causing a MISREADING of the base sequence (i.e., the gene).

TED OGA NDT HEB ATC ANE ATT HER AT_

• Autosomal or Sex-Linked? Recessive or Dominant? (NOTE: Traits expressed through family generations are easiest to follow).

Pedigrees

(A) Traits Controlled by a Single Allele• 200+ human traits are determined by a single allele, dominance or recessive (Ex: Cystic Fibrosis, Autosomal Recessive).

(1)Huntington’s Disease (Autosomal Dominant)• Expressed in 40’s LOSS of neuromuscular control and death.

(NOTE: depending on WHEN children are born, the disease may be UNKNOWINGLY passed from one generation to the next).

• Inability to BREAK DOWN the amino acid phenylalanine. (i.e., An ACCUMULATION of the amino acid may result in severe BRAIN DAMAGE).

(4) Phenylketonuria (PKU Autosomal Recessive)

NOTE: If positive, a phenylalanine-FREE diet will be REQUIRED from birth THROUGHOUT life.

(3) Duchenne Muscular Dystrophy (X-Linked Recessive)• Results in progressively WEAKENED and eventually DESTROYED muscle tissue. (males more vulnerable, females protected).

(2) Genetic Marker (associated gene for a disease)

(NOTE: Recently geneticists have discovered a genetic marker for the HD allele which has a 96% ACCURACY of PREDICTING its onset).

• A SHORT sequence of DNA that shows a CORRELATION with a particular DISEASED GENE nearby (an indicator of a trait or disease)

(E) Sex-INFLUENCED Traits (NOT Sex-Linked—genes are AUTOSOMAL)

• The presence of male or female SEX HORMONES influences the expression of certain human traits. (Ex: Pattern Baldness-B, b)

Ex: BB will lose their hair, Bb woman keeps hair, Bb man loses hair.NOTE: These differences in gene expression are due to HIGHER levels of TESTOSTERONE in men, which INTERACTS with the Bb genes to produce BALDNESS.