How Genes Are Transmitted from Generation to Generation

Chapter 4

Central Points

Genes are transmitted from generation to generation

Traits are inherited according to predictable rules

Gregor Mendel – The Father of Genetics

4.1 How Are Genes Transmitted?

Experiments with pea plants in 1800s

Traits, distinguishing characteristics

Specific patterns in the way traits were passed from parent to offspring

Different Plant Heights

Mendel’s Experiments

Some traits disappeared in the first generation of offspring (all tall)

Reappeared in 3:1 ratio (tall:short)

Dominant trait present in the first-generation offspring (tall)

Recessive trait absent in first generation but reappeared in the next generation (short)

Traits Are Passed by Genes

“Factors” or genes transmitted from parent to offspring

Each parent carries a pair of genes for a trait but contributes only one gene to each offspring

Separation of gene pair occurs during meiosis

Genes

Alleles: variations of a gene

Geneticists use letters for each allele.

Homozygous: identical alleles of a gene • TT or tt

Heterozygous: nonidentical alleles• Tt

Phenotype and Genotype

Phenotype: what an organism looks like• tall or short

Genotype: genetic makeup• TT, Tt, and tt

Identical phenotypes may have different genotypes• TT or Tt have tall phenotype

Mendel’s Law of Segregation

Two copies of each gene separate during meiosis

One copy of each gene in the sperm or egg

Each parent gives one copy of each gene

Sorting of Alleles

Mendel’s Law of Independent Assortment

Members of a gene pair segregate into gametes independently of other gene pairs

Gametes can have different combinations of parental genes

Human Traits: Albinism

Pigmentation dominant and lack of pigment recessive• AA, Aa: Pigmented• aa: Albino

Both parents Aa, each child has 25% chance of being albino (3:1 ratio)

Fig. 4-3a, p. 61

Aa × Aa

Aa Aa

A a A a

Two carriers of albinism have a child.

The male and female can contribute either an A allele or an a allele to the gamete.

Fig. 4-3b, p. 61

Genotype Phenotype

A a

1 AA

2 Aa3/4 normal coloring

AAA

normalAa

normal

1 aa 1/4 albinoa

Aa normal

aa albino

This shows the possible genotypes and phenotypes of the offspring.

The possible offspring and allele combinations are shown above.

Pedigree 1

Shows all family members and identifies those affected with the genetic disorder

Pedigree 2

Pedigree Symbols

p. 62

Male

Female

Mating

Mating between relatives (consanguinous)

I Parents and children. Roman numerals symbolize generations. Arabic numbers symbolize birth order within generation (boy, girl, boy)II

1 2 3

I, II, III, etc. = each generation 1, 2, 3, etc. = individuals within a generation

p. 62

or Unaffected individual

or Affected individual

or Known heterozygotes

or Proband; a person in family who is the focus of the pedigree

PP

I, II, III, etc. = each generation 1, 2, 3, etc. = individuals within a generation

Pedigree Symbols

Proband

Person who is the focus of the pedigree

Indicated by an arrow and the letter P

4.2 Examining Human Pedigrees

Determine trait has dominant or recessive inheritance pattern

Predict genetic risk for:• Pregnancy outcome• Adult-onset disorder• In future offspring

Three Possible Patterns of Inheritance

Autosomal recessive

Autosomal dominant

X-linked recessive

Autosomal on chromosomes 1–22

X-linked traits on the X chromosome

Autosomal Recessive

Unaffected parents can have affected children

All children of affected parents are affected

Both parents Aa, risk of affected child is 25%

~Equal affected male and female

Both parents must transmit the gene for a child to be affected

Autosomal Recessive Pedigree

Autosomal Recessive Genetic Disorders

Albinism A = normal coloring; a = albinism

Group of genetic conditions, lack of pigmentation (melanin) in the skin, hair, and/or eyes

Normally, melanin in pigment granules inside melanocytes

In albinism, melanocytes present but cannot make melanin

Oculocutaneous albinism type I (OCA1)

Cystic Fibrosis (CF)

C = normal; c = cystic fibrosis

CF affects glands that produce mucus and digestive enzyme

CF causes production of thick mucus in lungs blocks airways

Develop obstructive lung diseases and infections

Identified CF gene and protein (CFTR)

Sickle Cell Anemia (SCA)

S = normal red blood cells; s = sickle

High frequency in areas of West Africa, Mediterranean Sea, India

Abnormal hemoglobin molecules aggregate to form rods

Red blood cells, crescent- or sickle-shaped, fragile and break open

Normal and Sickled Cells

Autosomal Dominant (1)

Requires one copy of the allele (Aa) rarely present in a homozygous condition (AA)

aa: Unaffected individuals

Affected individual has at least one affected parent

Aa X aa: Each child has 50% chance of being affected

Autosomal Dominant (2)

~Equal numbers of affected males and females

Two affected individuals may have unaffected children

Generally, AA more severely affected, often die before birth or in childhood

Autosomal Dominant Pedigree

Autosomal Dominant Genetic Disorders

Animation: Chromosomes and Human Inheritance (autosomal-dominant inheritance)

Animation: Chromosomes and Human Inheritance (autosomal-recessive inheritance)

Neurofibromatosis (NF)

N = Neurofibromatosis 1; n = normal

Many different phenotypes

Café-au-lait spots, or noncancerous tumors in the nervous system can be large and press on nerves

Deformities of the face or other body parts (rarely)

NF gene has a very high mutation rate

Neurofibromatosis

Huntington Disease (HD) H = Huntington disease; h = normal

Causes damage in brain from accumulation of huntingtin protein

Symptoms begin slowly (30–50 years old)

Affected individuals may have already had children (50% chance with one Hh parent)

Progressive neurological signs, no treatment, die within 10–25 years after symptoms

Adult-Onset Disorders

Expressed later in life

Present problems in pedigree analysis, genetic testing may be required

Examples:• Huntington disease (HD)• Adult polycystic kidney disease (ADPKD)

Both examples are autosomal dominant

4.3 X-Linked Recessive Traits

Genes on X chromosome: X-linked

Genes on Y chromosome: Y-linked

For X-linked traits:• Females XX, XX*, or X*X*• Males XY or X*Y• Males cannot be homozygous or heterozygous,

they are hemizygous for genes on X• Distinctive pattern of inheritance

X-Linked Recessive Inheritance

Mother gives one X chromosome to offspring

Father gives X to daughters and Y to sons

Sons carry X from mother

For recessive traits, X*X* and X*Y affected

More males affected

Pedigrees: X-Linked Inheritance

X-Linked Recessive Genetic Disorders

Inheritance of X-Linked Disorder

Animation: Chromosomes and Human Inheritance (X-linked inheritance)

Duchenne Muscular Dystrophy (DMD) (1) XM = normal; Xm = muscular dystrophy

Most common form, affects ~1/3,500 males

Infants appear healthy, symptoms age ~1–6 years

Rapid, progressive muscle weakness

Usually must use a wheelchair by age 12

Death, age ~20 from respiratory infection or cardiac failure

Duchenne Muscular Dystrophy (DMD) (2)

DMD gene on the end of X chromosome

Encodes protein dystrophin that supports plasma membrane during contraction

If dystrophin absent or defective, cells are torn apart

Two forms: DMD, and less-serious Becker muscular dystrophy (BMD)

Cells of a Person with MD

Hemophilia

XH = normal; Xh = hemophilia

Lack of clotting: factor VIII in blood

Affected individuals hemorrhage, often require hospitalization to treat bleeding

Hemophilia A most common form of X-linked hemophilia

Females affected if XhXh, both parents must carry the trait

Factor VIII

1980s, half of all people with hemophilia became infected with HIV

Recombinant DNA technology now used to make clotting factors free from contamination