Chromosomes andHuman Genetics

Chapter 12

Genes

Units of information about heritable traits

In eukaryotes, distributed among

chromosomes

Each has a particular locus Location on a chromosome

Homologous Chromosomes

Homologous autosomes are identical in length, size, shape, and gene sequence

Sex chromosomes are nonidentical but still homologous

Homologous chromosomes interact, then segregate from one another during meiosis

Alleles

Different molecular forms of a gene

Arise through mutation

Diploid cell has a pair of alleles at each

locus

Alleles on homologous chromosomes may

be same or different

Studying Human Genetics

Studying Human Genetics is much more complicated than using other model systems (e.g. Pea Plants)

Humans reproduce slowly, have few offspring, and it is unethical to breed humans for experiments

There are many techniques that are used to study human genetics indirectly

Karyotypes Pedigree analysis Linkage maps

Karyotype

Picture of an individual’s chromosomes

Making a Karyotype: Metaphase chromosomes are fixed

and stained Chromosomes are photographed

through microscope Photograph of chromosomes is cut up

and arranged to form karyotype diagram

Sex Chromosomes

Autosomes

Karyotype

Sex Chromosomes

Discovered in late 1800s

Mammals, fruit fliesXX is female, XY is male

In other groups XX is female, XY male

Human X and Y chromosomes function as

homologues during meiosis

Sex Determination

X

X Y

X

XX

XY

XX

XY

X X

Y

X

x

x

eggs sperm

female(XX)

male(XY)

Figure 12.5Page 198

The Y Chromosome

Fewer than two dozen genes identified

One is the master gene for male sex

determination SRY gene (sex-determining region of Y)

SRY present, testes form

SRY absent, ovaries form

The X Chromosome

Carries more than 2,300 genes

Most genes deal with nonsexual traits

Genes on X chromosome can be expressed in both males and females

Pedigree

A chart showing the genetic connections between individuals

A genetic family tree Often groups of people whose heritage is well

documented or who are somewhat isolated from others are used to develop pedigrees. E.g. Icelanders, Mormons, Ashkenazi Jews, Amish,

Sardinians

Pedigree Symbols

male

female

marriage/mating

Individual showing trait being studied

sex not specified

generationI, II, III, IV...

offspring in order of birth, from left to right

I

II

III

IV

V

6 7

12

5,5 6,6

5,5 6,6

5,5 6,6

5,5 6,6

5,5 6,6

5,5 6,6

6,6 5,5

6,6 5,5

5,6 6,7

6,6 6,6*Gene not expressed in this carrier.

*

malefemale

Example: Pedigree of Polydactyly

Hemophilia

Polydactyly or Extra Digits

Linked Genes

Genes found on one type of chromosome Linked genes can assort separately from

on another only through crossing over The closer to genes are to each other on a

chromosome, the more tightly linked they are (i.e. the more likely they are to assort together during meiosis

A B C D

a b c d

A B C D

a b c d

A B c d

a b C D

Markers A & B are linked

Markers A & C are not linked

Full Linkage

x

AB ab

50% AB 50% ab

All AaBb

meiosis, gamete formation

Parents:

F1 offspring:

Equal ratios of two types of gametes:

AB

ab

AB

ab

ab

AB

Incomplete Linkage

Parents:

F1 offspring:

Unequal ratios of four types of gametes:

All AaCc

x

meiosis, gamete formation

AC acA

C A

C

AC

a

c

ac

Ac

aC

a

c

parental genotypes

recombinant genotypes

Crossover Frequency

Proportional to the distance that separates genes

Crossing over will disrupt linkage between A and B

more often than C and D

A B C D

Linkage mapping

Done by using known “landmarks” or markers on chromosomes

These markers are either genes or DNA fragments whose location has already been worked out

By watching how these markers are inherited by those with & without the disorder, geneticists can predict the location of the gene responsible for the disorder

If a gene and a marker are found together 100% of the time, they are completely linked

If a gene and a marker are found together 50% of the time they are completely unlinked

Human Genetic Conditions

A genetic abnormality is an uncommon or rare trait E.g. Polydactyly

A genetic disorder is an inherited condition that may cause medical problems E.g. Cystic Fibrosis

A syndrome is a set of symptoms that characterize a disorder E.g. Down Syndome

Human Genetic Abnormalities/Disorders Different patterns of inheritance are

observed depending on the condition:Autosomal Recessive InheritanceAutosomal Dominant InheritanceX-linked inheritance

Autosomal Recessive Inheritance

If parents are both

heterozygous, child will

have a 25% chance of

being affected

Albinism

Autosomal Dominant Inheritance

Trait typically appears in every generation

Huntington Disorder

Autosomal dominant allele Causes involuntary movements, nervous system

deterioration, death Symptoms don’t usually show up until person is

past age 30 People often pass allele on before they know

they have it

Achondroplasia

Autosomal dominant allele In homozygous form usually

leads to stillbirth Heterozygotes display a

type of dwarfism Have short arms and legs

relative to other body parts

Males show disorder more than females

Son cannot inherit disorder from his father

X-Linked Recessive Inheritance

Color Blindness

Hemophilia

Chromosomal Mutations

Duplication Deletion Inversion Translocation

Duplication

Gene sequence that is repeated several to

hundreds of times

Duplications occur in normal

chromosomes

May have adaptive advantageUseful mutations may occur in copy

Duplication

normal chromosome

one segment repeated

three repeats

Inversion

A linear stretch of DNA is reversed

within the chromosome

segments G, H, I become inverted

In-text figurePage 206

Translocation

A piece of one chromosome becomes attached to another nonhomologous chromosome

Most are reciprocal Philadelphia chromosome arose from a

reciprocal translocation between chromosomes 9 and 22

Translocation

one chromosome

a nonhomologouschromosome

nonreciprocal translocation

In-text figurePage 206

Deletion

Loss of some segment of a chromosome Most are lethal or cause serious disorder

Polyploidy

Individuals have three or more of each type of chromosome (3n, 4n)

Common in flowering plants Lethal for humans

99% die before birthNewborns die soon after birth

PolyploidyIndividuals have three or more of each type of chromosome (3n, 4n)

Common in flowering plants

Found in some fish & amphibians

Lethal for humans

Aneuploidy

Individuals have one extra or less chromosome

(2n + 1 or 2n - 1) Major cause of human reproductive

failure Most human miscarriages are

aneuploids

Nondisjunction

n + 1

n + 1

n - 1

n - 1chromosome alignments at metaphase I

nondisjunction at anaphase I

alignments at metaphase II anaphase II

Figure 12.17Page 208

Down Syndrome

Trisomy of chromosome 21 Mental impairment and a variety of

additional defects Can be detected before birth Risk of Down syndrome increases

dramatically in mothers over age 35

Aneuploidy

Having one extra or one less chromosome

Downs Syndrome trisomy 21

Turners Syndrome XO

Klinefelters XXY

Downs Syndrome

Trisomy and monosomy in sex chromosomes

Turner Syndrome

Inheritance of only one X (XO) 98% spontaneously aborted Survivors are short, infertile females

No functional ovariesSecondary sexual traits reducedMay be treated with hormones, surgery

Klinefelter Syndrome

XXY condition Results mainly from nondisjunction in

mother (67%) Phenotype is tall males

Sterile or nearly soFeminized traits (sparse facial hair, somewhat

enlarged breasts)Treated with testosterone injections

Turners Syndrome

Klinefelters Syndrome

Phenotypic Treatments

Symptoms of many genetic disorders can

be minimized or suppressed byDietary controls

Adjustments to environmental conditions

Surgery or hormonal treatments

Genetic Screening

Large-scale screening programs detect affected persons

Newborns in United States routinely tested for PKUEarly detection allows dietary intervention

and prevents brain impairment

Prenatal Diagnosis

Amniocentesis

Chorionic villus sampling

Fetoscopy

All methods have some risks

Prenatal Diagnosis

Amniocentesis Chorionic villus sampling