Human Pedigree and Genetic Disease

Gregor Mendel Thomas Bayes

Common Pedigree Symbols

Male

FemaleMarriage

Affected Female

Female Carrier of Sex-linked Recessive

Sex Unknown

Consanguineous Marriage

No Known Pregnancy

Unmarried

DeadDivorce and Remarried

Female Carrier (Heterozygous)

Common Pedigree Symbols

Pregnancy in Progress

3 Three Males

5Five Individuals (both sexes)

Dizygotic (nonidentical, fraternal) twins

Monozygotic (identical) twins

Spontaneous Abortion

Proband, propositus, or index case

Adopted Child

Bad DivorceFamous Kid

Triplets!

Happy new wife!

Mistakes in Meiosis

Examples:

– Down’s Syndrome (Trisomy-21)

– Klinefelter’s Syndrome

– Turner’s Syndrome

Chromosomes fail to separate properly during meiosis, i.e., nondisjunction

ANEUPLOIDY -- an abnormal number of chromosomes

Polygenic Inheritance

Most human characteristics are polygenic, meaning they are influenced by several genes, e.g. skin color influenced by 3-6 genes; also, eye color, height, hair color

Complex characters are those that are influenced strongly by both the environment and genes, e.g., diabetes, heart disease, stroke, skin color, height

More patterns of inheritance….. Multiple alleles - genes with three or more alleles, e.g.,

ABO blood groups Incomplete dominance – condition that results in a

display of a trait that is intermediate between the two parents

X-linked traits – determined by x-linked genes, e.g., color blindness

Sex-influenced traits – usually autosomal, e.g. baldness is influenced by testosterone

Single-allele traits – more than 200 human traits are governed by single dominant alleles, e.g., Huntington’s disease

Detecting Genetic Disease Genetic Screening – examination of a person’s genetic

makeup involving karyotypes, blood tests for certain proteins, or direct tests of DNA– 200 genetic disorders can be detected in the fetus– Amniocentesis – removal of amniotic fluid from the sac

that surrounds the fetus between the 14th and 16th week of pregnancy

– Chorionic villi sampling – sample of cells derived between the 8th and 10th week from the zygote - cells grow between the mother’s uterus and the placenta; cells chromosomes, and proteins analyzed

Detecting Genetic Disease

– Chorionic villi sampling – CVS can help identify chromosomal problems such as Down syndrome or other genetic diseases such as cystic fibrosis, Tay-Sachs disease and sickle cell anemia. CVS is considered to be 98% accurate in the diagnosis of chromosomal defects, such as Down syndrome.

Normal Female Karyotype

Normal Male Karyotype

Down’s Syndrome Smallest chromosomes with 1500 genes affected. Occurs in 1 out of every 800 babies.

– 40% congenital heart defects. Can result from maternal age or chromosome

defect.

Klinefelter’s Syndrome

Occurs in one out of every 1000 males. Results from extra X chromosome = XXY. Males tall, sterile, small testicles, and mentally

handicapped.

Turner’s Syndrome

Occurs in females. Results from XO condition. Female is short, sterile, and mentally impaired.

Single Gene Inheritance

Autosomal dominant traits– Huntington’s Disease on chromosome #4– Marfan Syndrome on chromosome #15– Breast Cancer on chromosomes #17

Pedigree Analysis

Autosomal recessive traits

– Tay-Sachs Disease on chromosome #15– Cystic Fibrosis on chromosome #7– Sickle Cell Anemia on chromosome #11

X-Linked Disease (Sex-Linked)

– Hemophilia --Duchenne’s muscular dystrophy– Color Blindness

Autosomal Dominant Traits

Present on any autosomal chromosome, i.e., 1-22.

One allele present = disease present, i.e., a person has it or he or she does not

Huntington’s Disease

Begins to show up by age 45-55, within 10-20 years, death is eminent.

Progressive degeneration of nervous system; irregular body movements and slurred speech.

If one parent has HD, offspring have 50% chance of inheriting disease.

Autosomal dominant on chromosome 4; 1 in 10,000 births

Huntington’s Disease

What are the genotypes of the parents?

Hh hh

Marfan Syndrome

Symptoms: long limbs, loose joints, deformed vertebral column, crowded teeth, rupture of large arteries

1 in 20,000 Americans born with it Caused by lack of fibrillin-1, a major

component of connective tissue found in ligaments and blood-vessel sheaths

Autosomal Recessive Disease manifests itself if offspring inherits

one recessive gene from each parent. If parents are carriers, 25% of offspring

will have disease.

Tay-Sachs Disease 1 in 600 Jews of European descent born with it Lipids deposited in nervous system, causing brain to be damaged -- blindness,

loss of movement, mental deterioration. No break down of cellular wastes in lysosome due to absence of

hexosaminidase A – mutation causes nerve death

Symptoms appear around 6 months of age and victims die due to paralysis and/or convulsions before the age of five.

Tay-Sachs Disease

What are the genotypes of all individuals in this family?

Tt Tt

tt

TtTt

TT or Tttt Tt or TTTt or TT

TT or Tt

Cystic Fibrosis Found in Caucasians.

– Most common lethal genetic disorder among white Americans.

– Autosomal recessive on chromosome 7 Thick mucus produced in lungs, intestines,

and pancreas.

1/20 of Caucasian population are carriers.– One in 2,000 children born to white Americans

inherits the disorder.– CF kills ~500 children and young adults each year.

Sickle Cell Anemia Found in both African Americans and Hispanics of

Carribbean ancestry (1 in 500 African Americans) Hemoglobin (oxygen-carrying protein) differs by ONE amino

acid.

Sickling of cells occurs, clogging vessels -- stroke. In U.S., 60,000 people have it; 30 million carriers. Autosomal recessive on chromosome 11

X-Linked Disorders

Found on the 23rd pair of chromosomes, i.e., the sex chromosomes.

Usually shows up in males due to Y chromosome lacking genes, i.e., one recessive gene in males produces disorder.

Mother carriers pass gene to sons.

Hemophilia -- “Bleeder’s Disease”

Deficient blood coagulation due to absence of coagulation factor 8 that helps cause blood to clot.

50% of daughters will also be carriers.

XHXh XHY

1 in 7,000 born with it X-linked recessive on chromosome X

Duchenne’s Muscular Dystrophy

Progressive destruction of muscles.

Patients wheelchair bound by teens.

Female carriers can be detected by presence of creatine kinase.

Can be detected by the 20th week of gestation.

Duchenne’s Muscular Dystrophy

XDXd XDY

Color Blindness

Red-Green Color Blindness

Multiple Alleles Blood type, using I gene. Human blood types include:

Phenotype Genotype–A IAIA or IAi–B IBIB or IBi–AB IAIB (Universal Recipient)–O ii (Universal Donor)

If a child has type O blood and its mother has type A, could a type B man be the father? Why couldn’t a blood test be used to prove he is the father?