NOTES: 14.1 -14.2 HUMAN HEREDITY • Key Terms – Autosomal Recessive – Autosomal Dominant – Pedigree – Tay -Sachs – Cystic Fibrosis – Phenylketonuria

• Key Concepts – How to read and interpret a pedigree – How diseases are caused Recessive and Dominant Alleles:

• Some common genetic disorders are autosomal recessive – This means that you need two recessive alleles (on any of the 44 chromosomes —NOT the sex chromosomes) to express the disease • EX: Cystic Fibrosis • Other genetic disorders are autosomal dominant – Only one allele is needed for the trait to be expressed • EX: Huntington’s Disease Autosomal Recessive Disorders:

• In order to develop an autosomal recessive trait, an individual must have the genotype: “ aa ” • To be born with a homozygous recessive genotype, both parents must be heterozygotes (“carriers”)…or homozygous recessive themselves (although with most disorders, that is not the case)…WHY NOT? From gene to molecule:

• In both cystic fibrosis and sickle cell anemia, a small change in the DNA of a single gene affects the structure of a protein, causing a serious genetic disorder Cystic Fibrosis:

• Caused by a recessive allele on chromosome #7 – It is an autosomal genetic disorder • Causes digestive and respiratory problems • Death around 20 -30 years of age • How does it happen? – Three bases are deleted from the protein, which removes one amino acid – The protein cannot fold properly anymore, and is destroyed – Result: airway is clogged with mucus

CF Example:

• Cystic fibrosis heterozygotes (Ff) – just one copy of the normal (dominant) allele is enough to supply the cell with the proper proteins to function. – Because of this, the normal allele is considered dominant over the recessive allele • Therefore, a person who is heterozygous does not suffer from Cystic Fibrosis Sickle Cell Anemia:

● One DNA base has been changed • Amino acid is valine , instead of glutamic acid • Result = abnormal hemoglobin • The abnormal hemoglobin forms crystal - like structures that change the shape of the red blood cells Sickle Cell Anemia: • The abnormal red blood cells are shaped like a “sickle” or a half-moon ; • These RBCs slow blood flow, block small blood vessels, and result in tissue damage and pain. Sickle Cell Anemia:

• Three genotypes possible: 1) HH = all healthy hemoglobin

2) Hh = ½ healthy hemoglobin; ½ abnormal hemoglobin; **CODOMINANCE !!

3) hh = all abnormal hemoglobin Sickle Cell Anemia:

• Individuals who are Hh do not have serious health problems and can lead relatively normal lives, but- • They do show some signs of sickle cell anemia if the availability of oxygen is reduced (i.e. high altitude; strenuous exercise) Pedigrees

• Graphical representation recording the line of ancestors – Family tree – Used for breeding animals (e.g. dogs, cats, horses) – Trace genetic disorders Pedigree Chart:

• Shows how a trait is transmitted from generation to generation • Each row is a generation • Circles represent females • Squares represent males – Shaded in: person expresses that trait – Half shaded in: person is only a carrier – Clear: person does not carry or express that trait Symbols to Pedigrees

Tay-Sachs Disease:

• Autosomal recessive disorder • Recessive allele results in the absence of an enzyme that normally breaks down lipids in the central nervous system • Without this enzyme, the lipids accumulate in the nervous system and the affected individual dies

Phenylketonuria (PKU):

• Autosomal recessive disorder; • Absence of an enzyme to break down the amino acid phenylalanine • The accumulation of phenylalanine causes damage to the nervous system • By avoiding phenylalanine in the diet, affected infants can avoid the symptoms of the disorder

Autosomal Recessive Traits & Pedigrees: • May skip a generation • Affected individuals are born to 2 carriers • Males and females affected equally • KNOWN carriers will be half -shaded in…it is not always possible to know if an individual is a carrier

What about autosomal dominant human traits? • A single dominant allele inherited from 1 parent is all that is needed for a person to show the dominant trait. Simple Dominant Traits:

• Tongue rolling • Unattached earlobes • Hitchhiker’s thumb • Hair in the middle section of fingers • Ability to taste PTC Autosomal Dominant Traits & Pedigrees: • Typically seen in every generation, affecting multiple people • Affected individuals are born to affected parent(s) • Males and females affected equally • There are NO “carriers”! (you either have it – AA or Aa – or you don’t – aa )

Autosomal Dominant Disorder: HUNTINGTON’S DISEASE • Rare, but lethal, dominant allele ; • Results in a breakdown of parts of the brain; • Onset between the ages of 30 and 50; • No known treatment or cure; • There is a test available to see if you have it – may help with the decision to start a family; • Every child of an affected individual has a 50/50 chance of being affected (and passing it down)

Sex-Linked Traits and Pedigrees:

• only (or mostly) males are affected ; • affected males are born to “carrier” females; • typically not seen in all generations

Queen Victoria’s Legacy in Royal Families of Europe