Genetic Disorders

When things don’t go right

Proteus Syndrome

Neurofibromatosis

Holoprosencephaly

Cystic Fibrosis

Tay-Sachs

Down’s Syndrome

ProgeriaMarfan

Angelman

Huntington’s Disease

Karyotype - a picture of chromosome pairs

It shows us chromosomes!1. Homologous chromosomes2. Autosomal Chromosomes3. Sex chromosomes

Pairing up chromosomes!1. Size2. Gene bands3. Location of centromere

Humans have:22 pairs of autosomes1 pair of sex chromosomes tells gender,total = 23 pairs or 46 chromosomes.

• Chromosomes are made up of _____ which are made up of ____ & ______ • Organisms’ chromosomes come in _______________ (one from mom, one from dad)

• Homologous pairs are evident during ______, where they then separate. • The location of a gene on the chromosome is called its ______• Traits can be expressed as different ________ at the gene locus

Homologous chromosomesGene loci for eye color

Allele for blue eyes (b)

Allele for brown eyes (B)

genes DNA proteinHomologous pairs

meiosislocus

alleles

Crossing Over• During Prophase 1

– Homologous chromosomes pair up (synapsis)– Tetrads of 4 sister chromatids intertwine – At the chiasma - homologous pairs swap

pieces of chromosome– crossing over results in more genetic diversity

tetrad

synapsis

chiasma

Chromosomal Disorders due to Nondisjunction• Homologous pairs are supposed to separate during anaphase I of Meiosis • Then their sister chromatids are supposed to separate during anaphase II of Meiosis• The number of chromosomes in gametes should be N (the haploid number)

Cell A Cell B

• Which is the most devastating? How many viable sperm for Cell A? cell B?

Sex Chromosome Disorders due to Nondisjunction

Autosomal Disorders due to Nondisjunction

Distinguish between:

Autosomal Disorders:a. Cystic fibrosisb. Tay-Sachs Diseasec. Sickle Cell Anemia

Sex-Linked Disorders: a. Color-blindnessb. Duchenne Muscular Dystrophyc. Hemophilia

• The most common inherited disease among Caucasians 1 out of 25 is a carrier. 

• Autosomal recessive

The Normal CFTR Protein in the Lungs:

Using active transport, a Cl- ion is pumped across the cell membrane of normal lung cells through a Cl- ion channel.

Cystic FibrosisCystic Fibrosis

The Cl- attracts water, which moistens the lung cell membrane, helping to produce a thin layer of mucus.

In one form of CF, a mutation in the DNA causes a binding site on the CFTR protein to change shape, and the ATP will not bind.

Cl-

P

ATP will not bind at the mutated site. Cl- can not leave the cell. A thick, stringy mucus builds up on the outside of the lung cell membrane.

The thick mucus provides a home to bacteria which cause deadly infections.

(7q31.2)

Tay-Sachs Disease

A rare autosomal recessive disorder of theHEX A gene on the long arm (q) of chromosome 15 between position 23 and 24

Warren Tay - Opthalmologist, who described the cherry-red spot on the retinaBernard Sachs - Neurologist, who first described the changes in the brain

Over 100 mutations have been identified in the HEX A gene - single base insertions, deletions, missense mutations, splice phase mutations where introns are not properly excised, etc. which alters the gene’s normal protein production of a lysosomal enzyme.

A progressive deterioration of nerve cells due to a build up of gangliosides in the brain’s nerve cells. Mental and physical deterioration begins around six months of age, often leading to death by age four.

Other Chromosome 15 Syndromes

Angelmann SyndromeRare genetic disease where genes on the maternal chromosome 15 are deleted or silenced. Seizures, jerky movements (hand-flapping), happy laughing, smiling demeanor, severe intellectual and developmental disabilities.

Prader-willi SyndromeRare genetic disease where 7 genes on the paternal chromosome 15 are deleted or silenced. Extreme and insatiable appetite- thus often become obese, narrow at the temple, poor muscle tone, cognitively IQ’s tend to range 35 - 85

Marfan SyndromeAn autosomal dominant disorder caused by a mutation in the FBN1 gene which produces fibrilin-1. Fibrillin-1 forms fibers in connective tissue and is supposed to bind to TGF-ß (a growth factor), keeping it sequestered. Without adequate Fibrillin-1, heart, blood vessels, bones, joints, and eyes are compromised.

Normal Red Blood Cells

Sickle CellsSickle Cells get

trapped in capillaries

A mutation occurs in the Beta Globin Gene and: The codon CTT is changed to CAT, so instead of making Glu (glutamic acid) --> it makes Val (valine)

1 amino acid change of 146 amino acids = Sickle Cell Anemia

An autosomal recessive disorder caused by a point mutation (substitution) on Chromosome 11 at the Beta Globin Gene, which is responsible for making hemoglobin, a complex protein structure in red blood cells - the iron-rich oxygen carrying molecule of the circulatory system in all vertebrates.

A. Sickle Cell AnemiaA. Sickle Cell Anemia

Heterozygous for sickle cell makes a person immune to Malaria because the presence of the protozoan (transported by the mosquito) causes the defective red blood cell to rupture before the protozoan can reproduce.

http://www.pbs.org/wgbh/evolution/library/01/2/l_012_02.html

The Gene for Red Green Vision is carried on the X Chromosome. It is an X-linked recessive disorder. One mutation causes Red-Green colorblindness--found almost exclusively in males.

What a person with normal color vision sees.

C. ColorblindnessC. Colorblindness

What a person with red green colorblindness sees.

R O Y G B I V Y G B I V

Women have an extra X chromosome, called a Barr Body, That can serve as a “back up” if the first is faulty

http://colorvisiontesting.com/How does the world look to acolor blind person?

Duchenne Muscular DystrophyA recessive, X-linked disorder caused by a mutation in the dystrophin gene where exons 45 to 54 the short arm (p) of the X chromosome at Xp21.2 are deleted.

Dystrophin is an important structural component within muscle tissue providing structural stability, without sufficient amounts, leads to muscle degeneration and eventually death.

HemophiliaA recessive, X-linked disorder caused by a mutation in the F8 gene (Classic Hemophilia A - Factor VIII deficiency) or F9 gene (Christmas Disease or Factor IX deficiency) where normal clotting proteins are either missing, lacking or ineffective in coagulation to seal damaged blood vessels and prevent excessive loss of blood.