Chromosomes and Human Inheritance

Chapter 12

Impacts, Issues:Strange Genes, Tortured Minds

Exceptional creativity often accompanies neurobiological disorders such as schizophrenia, autism, chronic depression, and bipolar disorder• Examples: Lincoln, Woolf, and Picasso

12.1 Human Chromosomes

In humans, two sex chromosomes are the basis of sex – human males have XY sex chromosomes, females have XX

All other human chromosomes are autosomes – chromosomes that are the same in males and females

Sex Determination in Humans

Sex of a child is determined by the father• Eggs have an X chromosome; sperm have X or Y

Sex Determination in Humans

The SRY gene on the Y chromosome is the master gene for male sex determination• Triggers formation of testes, which produce the

male sex hormone (testosterone)• Without testosterone, ovaries develop and

produce female sex hormones (estrogens)

Sexual Development in Humans

Fig. 12-2a, p. 186

diploid germ cells in female

diploid germ cells in male

meiosis, gamete formation in both female and male:

eggs sperm

X × Y

× XX

fertilization:

X X

X XX XX

Y XY XY

sex chromosome combinations possible in the new individual

Fig. 12-2bc, p. 186

Fig. 12-2bc, p. 186

At seven weeks, appearance of “uncommitted” duct system of embryo

At seven weeks, appearance of structures that will give rise to external genitalia

Y chromosome present

Y chromosome absent

Y chromosome present

Y chromosome absent

testes ovaries

10 weeks 10 weeks

ovary

penis vaginal opening

uterus

penis vagina

testis birth approaching

b c

Animation: Human sex determination

Karyotyping

Karyotype• A micrograph of all metaphase chromosomes in a

cell, arranged in pairs by size, shape, and length• Detects abnormal chromosome numbers and

some structural abnormalities

Construction of a karyotype• Colchicine stops dividing cells at metaphase• Chromosomes are separated, stained,

photographed, and digitally rearranged

Karyotyping

Fig. 12-3a, p. 187

Fig. 12-3b, p. 187

Animation: Karyotype preparation

12.1 Key ConceptsAutosomes and Sex Chromosomes

All animals have pairs of autosomes – chromosomes that are identical in length, shape, and which genes they carry

Sexually reproducing species also have a pair of sex chromosomes; the members of this pair differ between males and females

12.2 Autosomal Inheritance Patterns

Many human traits can be traced to autosomal dominant or recessive alleles that are inherited in Mendelian patterns

Some of those alleles cause genetic disorders

Autosomal Dominant Inheritance

A dominant autosomal allele is expressed in homozygotes and heterozygotes• Tends to appear in every generation• With one homozygous recessive and one

heterozygous parent, children have a 50% chance of inheriting and displaying the trait

• Examples: achondroplasia, Huntington’s disease

Autosomal Recessive Inheritance

Autosomal recessive alleles are expressed only in homozygotes; heterozygotes are carriers and do not have the trait• A child of two carriers has a 25% chance of

expressing the trait• Example: galactosemia

Autosomal Inheritance

Fig. 12-4a, p. 188

Fig. 12-4b, p. 188

Animation: Autosomal dominant inheritance

Animation: Autosomal recessive inheritance

Galactosemia

Neurobiological Disorders

Most neurobiological disorders do not follow simple patterns of Mendelian inheritance• Depression, schizophrenia, bipolar disorders

Multiple genes and environmental factors contribute to NBDs

12.3 Too Young to be Old

Progeria• Genetic disorder that results in accelerated aging• Caused by spontaneous mutations in autosomes

12.2-12.3 Key ConceptsAutosomal Inheritance

Many genes on autosomes are expressed in Mendelian patterns of simple dominance

Some dominant or recessive alleles result in genetic disorders

12.4 Examples of X-Linked Inheritance

X chromosome alleles give rise to phenotypes that reflect Mendelian patterns of inheritance

Mutated alleles on the X chromosome cause or contribute to over 300 genetic disorders

X-Linked Inheritance Patterns

More males than females have X-linked recessive genetic disorders• Males have only one X chromosome and can

express a single recessive allele• A female heterozygote has two X chromosomes

and may not show symptoms

Males transmit an X only to their daughters, not to their sons

X-Linked Recessive Inheritance Patterns

Animation: X-linked inheritance

Some X-Linked Recessive Disorders

Hemophilia A• Bleeding caused by lack of blood-clotting protein

Red-green color blindness• Inability to distinguish certain colors caused by

altered photoreceptors in the eyes

Duchenne muscular dystrophy• Degeneration of muscles caused by lack of the

structural protein dystrophin

Hemophilia A in Descendents of Queen Victoria of England

Red-Green Color Blindness

Fig. 12-9a, p. 191

Fig. 12-9b, p. 191

Fig. 12-9c, p. 191

Fig. 12-9d, p. 191

12.4 Key ConceptsSex-Linked Inheritance

Some traits are affected by genes on the X chromosome

Inheritance patterns of such traits differ in males and females

12.5 Heritable Changes in Chromosome Structure

On rare occasions, a chromosome’s structure changes; such changes are usually harmful or lethal, rarely neutral or beneficial

A segment of a chromosome may be duplicated, deleted, inverted, or translocated

Duplication

DNA sequences are repeated two or more times; may be caused by unequal crossovers in prophase I

p. 192

normal chromosome

one segment repeated

Deletion

Loss of some portion of a chromosome; usually causes serious or lethal disorders• Example: Cri-du-chat

p. 192

segment C deleted

Deletion: Cri-du-chat

Fig. 12-10a, p. 192

Fig. 12-10b, p. 192

Inversion

Part of the sequence of DNA becomes oriented in the reverse direction, with no molecular loss

p. 192

segments G, H, I become inverted

Translocation

Typically, two broken chromosomes exchange parts (reciprocal translocation)

p. 192

chromosome

nonhomologous chromosome

reciprocal translocation

Does Chromosome Structure Evolve?

Changes in chromosome structure can reduce fertility in heterozygotes; but accumulation of multiple changes in homozygotes may result in new species

Certain duplications may allow one copy of a gene to mutate while the other carries out its original function

Differences Among Closely Related Organisms

Humans have 23 pairs of chromosomes; chimpanzees, gorillas, and orangutans have 24• Two chromosomes

fused end-to-end

Fig. 12-11, p. 193

human chimpanzee gorilla orangutan

Evolution of X and Y Chromosomes from Homologous Autosomes

Fig. 12-12, p. 193

Ancestral reptiles Ancestral reptiles Y X

Monotremes Y X

Marsupials Y X

Monkeys Y X

Humans Y X(autosome pair)

areas that can cross over

areas that cannot cross over

SRY

A Before 350 mya, sex was determined by temperature, not by chromosome differences.

B SRY gene evolves 350 mya. Other mutations accumulate and the chromosomes of the pair diverge.

C By 320–240 mya, the two chromosomes have diverged so much that they no longer cross over in one region. The Y chromosome begins to degenerate.

D Three more times, 170–130 mya, the pair stops crossing over in another region. Each time, more changes accumulate, and the Y chromosome gets shorter. Today, the pair crosses over only at a small region near the ends.

12.6 Heritable Changes in the Chromosome Number

Occasionally, new individuals end up with the wrong chromosome number• Consequences range from minor to lethal

Aneuploidy• Too many or too few copies of one chromosome

Polyploidy• Three or more copies of each chromosome

Nondisjunction

Changes in chromosome number can be caused by nondisjunction, when a pair of chromosomes fails to separate properly during mitosis or meiosis

Affects the chromosome number at fertilization• Monosomy (n-1 gamete)• Trisomy (n+1 gamete)

Nondisjunction

Autosomal Change and Down Syndrome

Only trisomy 21 (Down syndrome) allows survival to adulthood• Characteristics include physical appearance,

mental impairment, and heart defects

Incidence of nondisjunction increases with maternal age

Can be detected through prenatal diagnosis

Trisomy 21

Fig. 12-13b, p. 194

n + 1

n + 1

n − 1

n − 1

chromosome alignments at metaphase I

NONDISJUNCTION AT ANAPHASE I

alignments at metaphase II

CHROMOSOME NUMBER

IN GAMETESanaphase II

Fig. 12-13b, p. 194

chromosome alignments at metaphase I

NONDISJUNCTION AT ANAPHASE I

alignments at metaphase II

n + 1

n + 1

n − 1

n − 1

CHROMOSOME NUMBER

IN GAMETESanaphase IIStepped Art

Down Syndrome and Maternal Age

Fig. 12-14a, p. 195

Fig. 12-14b, p. 195

Change in Sex Chromosome Number

Changes in sex chromosome number may impair learning or motor skills, or be undetected

Female sex chromosome abnormalities• Turner syndrome (XO)• XXX syndrome (three or more X chromosomes)

Male sex chromosome abnormalities• Klinefelter syndrome (XXY)• XYY syndrome

Turner Syndrome

XO (one unpaired X chromosome)• Usually caused by

nondisjunction in the father

• Results in females with undeveloped ovaries

12.5-12.6 Key Concepts: Changes in Chromosome Structure or Number

On rare occasions, a chromosome may undergo a large-scale, permanent change in its structure, or the number of autosomes or sex chromosomes may change

In humans, such changes usually result in a genetic disorder

12.7 Human Genetic Analysis

Charting genetic connections with pedigrees reveals inheritance patterns for certain alleles

Pedigree• A standardized chart of genetic connections• Used to determine the probability that future

offspring will be affected by a genetic abnormality or disorder

Studying Inheritance in Humans

Genetic studies can reveal inheritance patterns or clues to past events • Example: A link

between a Y chromosome and Genghis Khan?

Defining Genetic Disorders and Abnormalities

Genetic abnormality• A rare or uncommon version of a trait; not

inherently life threatening

Genetic disorder• An inherited condition that causes mild to severe

medical problems, characterized by a specific set of symptoms (a syndrome)

Some Human Genetic Disorders and Genetic Abnormalities

Table 12-1, p. 196

Stepped Art

Recurring Genetic Disorders

Mutations that cause genetic disorders are rare and put their bearers at risk

Such mutations survive in populations for several reasons• Reintroduction by new mutations• Recessive alleles are masked in heterozygotes• Heterozygotes may have an advantage in a

specific environment

A Pedigree for Huntington’s Disease

A progressive degeneration of the nervous system caused by an autosomal dominant allele

Constructing a Pedigree for Polydactyly

Animation: Pedigree diagrams

12.8 Prospects in Human Genetics

Genetic analysis can provide parents with information about their future children

Genetic counseling• Starts with parental genotypes, pedigrees, and

genetic testing for known disorders• Information is used to predict the probability of

having a child with a genetic disorder

Prenatal Diagnosis

Tests done on an embryo or fetus before birth to screen for sex or genetic problems• Involves risks to mother and fetus

Three types of prenatal diagnosis• Amniocentesis • Chorionic villus sampling (CVS)• Fetoscopy

Amniocentesis

Animation: Amniocentesis

Fetoscopy

Preimplantation Diagnosis

Used in in-vitro fertilization• An undifferentiated cell is removed from the early

embryo and examined before implantation

After Preimplantation Diagnosis

When a severe problem is diagnosed, some parents choose an induced abortion

In some cases, surgery, prescription drugs, hormone replacement therapy, or dietary controls can minimize or eliminate symptoms of a genetic disorder• Example: PKU can be managed with dietary

restrictions

Genetic Screening

Genetic screening (widespread, routine testing for alleles associated with genetic disorders)• Provides information on reproductive risks• Identifies family members with a genetic disorder• Used to screen newborns for certain disorders • Used to estimate the prevalence of harmful

alleles in a population

12.7-12.8 Key ConceptsHuman Genetic Analysis

Various analytical and diagnostic procedures often reveal genetic disorders

What an individual, and society at large, should do with the information raises ethical questions

Animation: Deletion

Animation: Duplication

Animation: Inversion

Animation: Morgan’s reciprocal crosses

Animation: Translocation

Video: Strange genes, richly tortured minds