Human Genetics:Human Genetics:Genetic DisordersGenetic Disorders

Ms. Y. MartinezMs. Y. Martinez

LSHSLSHS

07-0807-08

Genes and the Environment Genes and the Environment 

The The phenotypephenotype of an organism is only of an organism is only partly determined by its partly determined by its genotypegenotype. .

Many traits are strongly influenced by Many traits are strongly influenced by environmentalenvironmental, or nongenetic, , or nongenetic, factors, including nutrition, exercise factors, including nutrition, exercise and sunlight. and sunlight.

For example, nutritional For example, nutritional improvements in the United States improvements in the United States and Europe have increased the and Europe have increased the average height of these populations average height of these populations about 10 centimeters over their about 10 centimeters over their average height in the 1800s. average height in the 1800s.

Human Genetic DisordersHuman Genetic Disorders

Most of the time, the mechanisms Most of the time, the mechanisms that separate human chromosomes that separate human chromosomes in meiosis work very well, but every in meiosis work very well, but every now and then something goes wrong. now and then something goes wrong.

The most common error in meiosis occurs The most common error in meiosis occurs when homologous chromosomes fail to when homologous chromosomes fail to separate. This is known as separate. This is known as nondisjunctionnondisjunction, which means “not , which means “not coming apart.” coming apart.”

If If nondisjunction nondisjunction occurs, abnormal occurs, abnormal numbers of chromosomes may find their numbers of chromosomes may find their way into gametes, and a disorder of way into gametes, and a disorder of chromosome numbers may result. chromosome numbers may result.

At the end of At the end of meiosis, the meiosis, the chromosomeschromosomes have failed have failed to separate to separate and the and the gametes gametes have an have an UNEQUAL UNEQUAL number of number of chromosomeschromosomes

After nondisjunction After nondisjunction occurs and a gamete occurs and a gamete has one has one EXTRAEXTRA chromosome, a chromosome, a TrisomicTrisomic human human genetic disorder can genetic disorder can result.result.

After nondisjunction After nondisjunction occurs and a gamete occurs and a gamete has one has one LESSLESS chromosome, a chromosome, a MONOSOMIC MONOSOMIC human human genetic disorder can genetic disorder can result.result.

Trisomy DisordersTrisomy Disorders

Remember 2n = 46Remember 2n = 46 In a trisomy disorder, a gamete has In a trisomy disorder, a gamete has

gained an EXTRA chromosomegained an EXTRA chromosome So, a trisomic individual has 2n = 47So, a trisomic individual has 2n = 47

Trisomy DisordersTrisomy Disorders

Trisomy 21 (Down or Down’s Trisomy 21 (Down or Down’s Syndrome)Syndrome)

Klinefelter (or Klinefelter’s) Syndrome Klinefelter (or Klinefelter’s) Syndrome (Males only, XXY Trisomy)(Males only, XXY Trisomy)

2n = 47

Trisomy 21, Down Trisomy 21, Down SyndromeSyndrome

Individuals Individuals have an have an extra 21extra 21stst chromosomchromosome e

Usually Usually occurs once occurs once in every 800 in every 800 birthsbirths

People People with with Down Down SyndromSyndromee

CharacteristicsCharacteristics Round faceRound face Extra 21Extra 21stst

chromosomechromosome Short fingersShort fingers Cupped earCupped ear Protruding Protruding

tonguetongue Mental Mental

deficiencydeficiency

Simian Simian Crease in Crease in the handthe hand

NondisjunctioNondisjunction n is the is the causecause

Incidence of Down Syndrome Incidence of Down Syndrome in Newborns in Newborns (Hook, et al., 1988)(Hook, et al., 1988)

Maternal Age

Incidence20 – 24 1 : 1400

25 – 29 1 : 1100

30 - 34 1 : 700

35 1 : 350

37 1 : 225

39 1 : 140

41 1: 85

43 1: 50

45+ 1 :25

Klinefelter Syndrome, XXY Klinefelter Syndrome, XXY TrisomyTrisomy

Individuals Individuals have an have an extra “X” extra “X” sex sex chromosomchromosome e

Usually Usually occurs once occurs once in every in every 1080 births1080 births

A male with A male with Klinefelter Klinefelter SyndromeSyndrome

Male Male reproductive reproductive cells do not cells do not undergo meiosis undergo meiosis (sterile)(sterile)

Only 40% have Only 40% have breast breast developmentdevelopment

Intelligence is Intelligence is less than normalless than normal

Nondisjunction is Nondisjunction is the causethe cause

Monosomy DisordersMonosomy Disorders

Remember 2n = 46Remember 2n = 46 In a monosomy disorder, a gamete In a monosomy disorder, a gamete

has LOST a chromosomehas LOST a chromosome So, a monosomic individual has 2n = So, a monosomic individual has 2n =

4545

Monosomy DisordersMonosomy Disorders Turner Syndrome, XO Turner Syndrome, XO

(Females Only)(Females Only) OROR Turner Syndrome , X Turner Syndrome , X

(Females only)(Females only)

2n = 45

Turner Syndrome, X or XOTurner Syndrome, X or XO

Individuals Individuals have only ONE have only ONE “X” sex “X” sex chromosome chromosome

Usually occurs Usually occurs once in every once in every 5000 births5000 births

A female with A female with Turner Turner SyndromeSyndrome

Female Female reproductive reproductive cells do not cells do not undergo undergo meiosis (sterile)meiosis (sterile)

Has webbing of Has webbing of the neckthe neck

Intelligence is Intelligence is less than less than normalnormal

Nondisjunction Nondisjunction is the causeis the cause

Autosomal Dominant Disorders Autosomal Dominant Disorders (ex RR, Rr)(ex RR, Rr)

Autosomal dominant is one of several Autosomal dominant is one of several ways that a trait or disorder can be ways that a trait or disorder can be passed down through families. passed down through families.

If a disease is If a disease is autosomal dominantautosomal dominant, it , it means you only need to get the means you only need to get the abnormal gene from one parent in order abnormal gene from one parent in order for you to inherit the disease. One of the for you to inherit the disease. One of the parents may often have the disease. parents may often have the disease.

Examples of Examples of Autosomal Autosomal Dominant Disorders (ex RR, Rr)Dominant Disorders (ex RR, Rr)

Huntington’s DiseaseHuntington’s Disease AchondroplasiaAchondroplasia PolydactylyPolydactyly Marfan SyndromeMarfan Syndrome

Huntington’s Disease, Huntington’s Disease, DD or DdDD or Dd

Huntington's disease causes a Huntington's disease causes a progressive loss of muscle control and progressive loss of muscle control and mental function until death occurs. mental function until death occurs.

People who have this disease generally People who have this disease generally show no symptoms until they are in show no symptoms until they are in their thirties or older, when the gradual their thirties or older, when the gradual damage to the nervous system begins. damage to the nervous system begins.

Achondroplasia, DD or DdAchondroplasia, DD or Dd

Most people with Most people with achondroplasia achondroplasia are born to are born to parents of average height, parents of average height, following a genetic change - following a genetic change - usually in the sperm. usually in the sperm.

This particular change - or This particular change - or mutationmutation - occurs - occurs occasionally when the DNA occasionally when the DNA is copied in cells that is copied in cells that multiply to make the sperm. multiply to make the sperm.

The mutation that causes The mutation that causes achondroplasia is a single achondroplasia is a single change in the letters of the change in the letters of the DNA code of the FGFR-3 DNA code of the FGFR-3 gene.gene.

CharacteristicsCharacteristics

short statureshort stature short arms short arms short legs short legs a large heada large head

Polydactyly, DD or DdPolydactyly, DD or Dd

PolydactylyPolydactyly refers refers to extra digits - in to extra digits - in the hand, extra the hand, extra fingers or thumbs. fingers or thumbs.

Marfan Syndrome, DD or DdMarfan Syndrome, DD or DdMarfan Marfan syndrome is a syndrome is a disorder that disorder that affects affects connective connective tissue. tissue. Connective Connective tissues are tissues are proteins that proteins that support skin, support skin, bones, blood bones, blood vessels and vessels and other organs. other organs.

CharacteristicsCharacteristics very tallvery tall ThinThin Double jointedDouble jointed heart and blood vessel heart and blood vessel

problemsproblems a weak in the aortaa weak in the aorta

President President Abraham Abraham Lincoln was Lincoln was thought to thought to have Marfan have Marfan Syndrome.Syndrome.

What do you What do you think?think?

Autosomal Recessive Disorders Autosomal Recessive Disorders (ex rr)(ex rr)

Autosomal recessive is one of several Autosomal recessive is one of several ways that a trait, disorder, or disease ways that a trait, disorder, or disease can be passed down through can be passed down through families.families.

An An autosomal recessiveautosomal recessive disorder disorder means two copies of an abnormal means two copies of an abnormal gene must be present in order for the gene must be present in order for the disease or trait to develop.disease or trait to develop.

Autosomal Recessive Disorders Autosomal Recessive Disorders

(ex rr)(ex rr) Phenylketonuria Phenylketonuria (fen-ul-ket-oh-NOOR-ee-uh),(fen-ul-ket-oh-NOOR-ee-uh), , ,

PKUPKU Cystic FibrosisCystic Fibrosis Tay-Sachs DiseaseTay-Sachs Disease Sickle-cell AnemiaSickle-cell Anemia AlbinismAlbinism

Phenylketonuria, PKU, (ex Phenylketonuria, PKU, (ex rr)rr)

Phenylketonuria (PKU) is a genetic Phenylketonuria (PKU) is a genetic disorder that is characterized by an disorder that is characterized by an inability of the body to utilize the inability of the body to utilize the essential amino acid, essential amino acid, phenylalaninephenylalanine. .

Phenylalanine is an amino acid found Phenylalanine is an amino acid found in milk and many other foods.in milk and many other foods.

If it goes untreated, it causes If it goes untreated, it causes “mental retardation.” “mental retardation.” (http://www.marchofdimes.com/professionals/14332_1219.asp) (http://www.marchofdimes.com/professionals/14332_1219.asp)

Cystic Fibrosis, (ex rr)Cystic Fibrosis, (ex rr) Is a common genetic disease that is Is a common genetic disease that is

most common among people whose most common among people whose ancestors came from Northern Europe. ancestors came from Northern Europe.

The disease is caused by a recessive The disease is caused by a recessive allele on chromosome 7. allele on chromosome 7.

Children with cystic fibrosis have serious Children with cystic fibrosis have serious digestive problems. In addition, they digestive problems. In addition, they produce a thick, heavy mucus that clogs produce a thick, heavy mucus that clogs their lungs and breathing passageways. their lungs and breathing passageways.

Tay-Sachs Disease, (ex rr)Tay-Sachs Disease, (ex rr)

Is caused by an allele found Is caused by an allele found mostly in Jewish families of mostly in Jewish families of central and eastern central and eastern European ancestry. European ancestry.

Tay-Sachs disease results in Tay-Sachs disease results in nervous system breakdown nervous system breakdown and death in the first few and death in the first few years of life. years of life.

Although there no treatment Although there no treatment for Tay-Sachs disease.for Tay-Sachs disease.

Sickle Cell DiseaseSickle Cell Disease Is a common genetic disorder found in African Is a common genetic disorder found in African

Americans. Americans. Is characterized by the bent and twisted shape of Is characterized by the bent and twisted shape of

the red blood cells.the red blood cells. These sickle-shaped red blood cells tend to get These sickle-shaped red blood cells tend to get

stuck in the capillaries, the narrowest blood vessels stuck in the capillaries, the narrowest blood vessels in the body.in the body.

As a result, blood stops moving through these As a result, blood stops moving through these vessels, damaging cells, tissues, and organs. vessels, damaging cells, tissues, and organs.

Sickle cell disease produces physical weakness and Sickle cell disease produces physical weakness and damage to the brain, heart, and spleen. In some damage to the brain, heart, and spleen. In some cases, it may be fatal.cases, it may be fatal.

Hemoglobin is the protein in Hemoglobin is the protein in red blood cells that carries red blood cells that carries oxygen. oxygen.

The normal allele for the The normal allele for the gene differs little from the gene differs little from the sickle cell allele—just one sickle cell allele—just one DNA base is changed. DNA base is changed.

This change substitutes the This change substitutes the amino acid valine for amino acid valine for glutamic acid. glutamic acid.

As a result, the abnormal As a result, the abnormal hemoglobin is somewhat less hemoglobin is somewhat less soluble than normal soluble than normal hemoglobin. hemoglobin.

Albinism, (ex rr)Albinism, (ex rr)

Albinism, (ex rr)Albinism, (ex rr)

Is an inherited condition present at Is an inherited condition present at birth, characterized by a lack of birth, characterized by a lack of pigment that normally gives color to pigment that normally gives color to the skin, hair, and eyes. the skin, hair, and eyes.

Many types of albinism exist.Many types of albinism exist. The condition, which is found in all The condition, which is found in all

races, may be accompanied by eye races, may be accompanied by eye problems and may lead to skin problems and may lead to skin cancer later in life. cancer later in life.

Sex-Linked Recessive Sex-Linked Recessive DisordersDisorders

(ex XrXr or XrY)(ex XrXr or XrY) Sex-linked diseases are inherited through Sex-linked diseases are inherited through

one of the "sex chromosomes" -- the X or Y one of the "sex chromosomes" -- the X or Y chromosomes. chromosomes.

Because these chromosomes determine Because these chromosomes determine sex, genes located on them are said to be sex, genes located on them are said to be sex-linked genessex-linked genes..

Many sex-linked genes are found on the X Many sex-linked genes are found on the X chromosome.chromosome.

Are found more often in Males (XY Are found more often in Males (XY makeup)makeup)

If mom is a If mom is a carrier carrier and dad and dad is is normalnormal, what , what chance will:chance will:

their daughters their daughters be be carrierscarriers?___?___

their daughters their daughters express express the the disorder?____disorder?____

their sons their sons expressexpress the the disorder?____disorder?____

their sons be their sons be carrierscarriers of the of the disorder?____disorder?____

Colorblindness, XrXr or XrYColorblindness, XrXr or XrY The gene associated with color vision is The gene associated with color vision is

located on the X chromosome. located on the X chromosome. In males, a defective version of this gene In males, a defective version of this gene

produces produces colorblindnesscolorblindness, an inability to , an inability to distinguish certain colors. distinguish certain colors.

The most common form of this disorder, The most common form of this disorder, red-green colorblindness, is found in about red-green colorblindness, is found in about 1 in 10 males in the United States. 1 in 10 males in the United States.

Among females, however, colorblindness Among females, however, colorblindness is rare—only about 1 female in 100 has is rare—only about 1 female in 100 has colorblindness. Why the difference? colorblindness. Why the difference?

A non-A non-colorblind colorblind individual individual will be will be able to see able to see the the number. A number. A colorblind colorblind individual individual will not.will not.

A colorblind A colorblind individual individual will not see will not see the green the green leaf.leaf.

A non-A non-colorblind colorblind individual individual will it.will it.

Hemophilia, XrXr or XrYHemophilia, XrXr or XrY

In hemophilia, a protein necessary for In hemophilia, a protein necessary for normal blood clotting is missing.normal blood clotting is missing.

About 1 in 10,000 males is born with a About 1 in 10,000 males is born with a form of hemophilia. form of hemophilia.

People with hemophilia can bleed to death People with hemophilia can bleed to death from minor cuts and may suffer internal from minor cuts and may suffer internal bleeding from bumps or bruises. bleeding from bumps or bruises.

Hemophilia can be treated by injections of Hemophilia can be treated by injections of normal clotting proteins, which are now normal clotting proteins, which are now produced using recombinant DNA. produced using recombinant DNA.

Czar Nicholas II of Czar Nicholas II of Russia and his Russia and his family, family, photographed c. photographed c. 1916, showing his 1916, showing his wife Alexandra wife Alexandra (who was a carrier (who was a carrier of hemophilia), his of hemophilia), his four daughters, four daughters, and (in the and (in the foreground) his son foreground) his son Alexis, perhaps the Alexis, perhaps the most famous most famous European royal European royal with hemophilia. with hemophilia.

Duchenne Muscular Duchenne Muscular Dystrophy, Dystrophy, XrXr or XrY XrXr or XrY

  Duchenne muscular dystrophy (DIS-Duchenne muscular dystrophy (DIS-truh-fee) is a sex-linked disorder that truh-fee) is a sex-linked disorder that results in the progressive weakening results in the progressive weakening and loss of skeletal muscle. and loss of skeletal muscle.

In the United States, one out of every In the United States, one out of every 3000 males is born with this 3000 males is born with this condition. condition.

In In DuchennDuchenne e muscular muscular dystrophdystrophy, y, posture posture changes changes as the as the child child grows.grows.

Human GenesHuman Genes The The humanhuman genomegenome—our complete set of —our complete set of

genetic information—includes tens of genetic information—includes tens of thousands of genes. thousands of genes.

The DNA sequences on these genes carry The DNA sequences on these genes carry information for specifying many information for specifying many characteristics, from the color of your eyes to characteristics, from the color of your eyes to the detailed structures of proteins within your the detailed structures of proteins within your cells. cells.

The exploration of the human genome has The exploration of the human genome has been a major scientific undertaking. By 2003, been a major scientific undertaking. By 2003, the DNA sequence of the human genome was the DNA sequence of the human genome was complete.complete.

Gene TherapyGene Therapy

    In gene therapy, an absent or In gene therapy, an absent or faulty gene is replaced by a faulty gene is replaced by a normal, working gene.normal, working gene.

Why? So the body can make the Why? So the body can make the correct protein or enzyme it needs, correct protein or enzyme it needs, which eliminates the cause of the which eliminates the cause of the disorder.disorder.

Gene TherapyGene Therapy