chapter 12 - the chromosomal basis of inheritance

Chromosome theory of inheritance

That genes have specific loci (positions) along chromosomes and that’s chromosomes undergo segregation and independent assortment

why did Thomas Morgan choose fruit flies (drosophila) as his experimental organism

• single mating results in hundreds of offsprings

• New generation every two weeks

• easily distinguishable by light microscopy due to having 4 chromosomes

• Sex determined by X and Y chromosomes like humans

Mutant phenotypes

• Due to changes in the original wild type gene sequence

• Alleles are indicated by a lower case letter for mutant and with a subscript + added for wild type

• Usually dominant but not always

Morgan’s first experiment conclusions

1. White eyed allele must be recessive as all of the F1 generation had red eyes when parent gen were homozygous for both colours

2. White allele must be located on the X chromosome since no females had white eyes

Morgans contribution to sex linked trait

• Correlated sex of an individual organisms with the presence of a specific trait is a sex linked trait

• Demonstrated unique inheritance patterns for sex linked traits

• Pattern of inheritance is dependant on who starts with the mutation either maternal or paternal

• Provided support for the chromosomal basis of inheritance

Pseudoautosomal

• Y chromosomes contain small regions at either end that are homologus to the X chromosome

• This allows it to act homologus to the X chromosomes

• They’re called pseudoautosomal as they act similar to autosomes

What do early embryo contain

Generic gonads with anatomical signs of sex appearing at 2 months. This is determined largely by the presence or absence of the Y chromosome in humans

What is SRY

This is the sex determine region of the Y chromosome that codes for a protein involved in the regulation of other genes involved in sex determination.

What happens if you dont have SRY

The absence of this gene product Results in the development of ovaries

Y linked genes

• 78 genes encoding for 25 proteins

• Half are expressed in the testes and are involved in testicular function and sperm production

• Very few Y linked disorders

X linked genes

• 1110 genes on the X chromosomes

• Recessive X linked disorders are rare in females (XX) as they need 2 affected alleles to show compared to males (XY)

• Males are hemizygous and only need one affected allele to show

Paternal vs maternal inheritance

Paternal - sperm donors will always pass on an X linked recessive allele to their XX progeny and not their XY

Maternal - Egg donors can pass an X linked recessive to both types of progeny

Duchenne muscular dystrophy

• 1/3500 XY individuals in the US are affected by

• Progressive weakening of muscles and loss of coordination due to absence of muscle protein, dystrophin

• Rarely live past early 20s if untreated

• X linked disorders

Hemophilia

• absence of one or more proteins involved in blood clotting

• Documented in royal families in Europe

• Treated with IV injections

• X linked disorders

X inactivation

• turns off one X chromosome in every female cell to balance gene expression with males

• The inactivated X forms a barr body, highly condensed chromosome that get reactivated again in egg gamete formation

• This occurs randomly and independently in each embryonic cell

What is XIST and its role in X inactivation

• during early embryonic development one X chromosome is randomly chosen to activate the XIST gene

• The XIST gene coats and silences that chromosome to initiate inactivation

How are XX individuals mosaics

Because X inactivation is random, XX individuals who are heterozygous for an X linked trait become mosaics, with different groups of cells expressing different alleles which produces patchy traits

Ex. Calico cats

Linked genes

Linked genes are genes located close together on the same chromosome making crossing over unlikely. This results in allelic combinations remaining the same as parents

Recombination of unlinked genes

When 2 genes are unlinked they assort independently during meiosis producing 1:1:1:1 Ratio of offspring in a dihybrid cross test cross. This results in 50% parental types and 50% recombinant type combinations of alleles

Linked genes frequencies

Linked genes demonstrate frequencies of parental phenotypes between 50-100% with a test cross

How to calculate for recombination frequencies and its relation to incomplete linkage

Recombination frequency = recombinants / total offspring X 100

• if below 50% but greater than 0%, it suggests incomplete linkage

Mapping gene distance

• assumes that the chance of crossing over at any point of the chromosomes is equal to

• Predicts that the further apart the two genes were the higher chance of crossing over occurs

• Uses test cross data to determine recombination frequencies between genes

Linkage map conversions

1 map unit = 1 centimorgan = 1% recombination frequency

Linkage map advantage and disadvantage

Advantage - allow for comparison of several different genes at once

Disadvantage - if genes are too far apart, crossing over is almost certain to occur. Leading to indistinguishable results from genes on separate chromosomes

Nondisjunction

Improper separation of homologus chromosomes in meiosis I or sister chromatids in meiosis II. Leading to gametes with too many or too few chromosomes

Aneuploidy

zygote that has an abnormal number of chromosomes

• due to fertilization of gametes with nondisjunction

• most common reason for early stage of pregnancy loss

Types of aneuploidy

Monosomic- zygote containing a single copy

Trisomic - zygote containing 3 copies

Polyploidy

• organisms with more than 2 complete copies of chromosome sets in all somatic cells

• tolerated by some organisims but not humans

Types of polyploidy

Triploidy (3n) - results from fertilization of an abnormal diploid egg

Tetraploidy (4n) - may result from failure of a zygote to divide following replication of its genome

Alterations in chromosome structure

Caused by errors in meiosis or damage which causes breakage of a chromosome

4 types of chromosome structure alterations

1. Deletion

2. Duplication

3. Inversion

4. Translocation

Deletion alteration

• most commonly found due to errors in meiosis

• Due to unequal crossing over

Duplication

• may also occur due to the attachment of a fragment from a non sister chromatid

Inversion alteration

• occurs when a fragment is inserted in the reverse direction

• Copy number of each gene is normal but regulation of genes may be altered.

• Potentially harmful to organism

Translocation and its 2 types

Reciprocal translocation - exchange of genetic segments between 2 non homologus chromosomes

• save copy number of genes

• May alter regulation

Non reciprocal translocation - transfer of segment of one chromosome to another non homologus chromosome with nothing in return

• leads to gametes errors

Fetal testing and what its used for

• used to create karyotypes by taking cell samples and induces them to divide

• Cells are then analyzed in metaphase to create a karyotype

Examples of fetal testing

Amniocentesis and chorionic villus sampling

Aneuploidy and human disorder

Individuals with aneuploidy exhibit specific sets of traits or syndrome which are associated with their condition

Ex. Trisomy 21 - Down syndrome

Maternal age and its effects to aneuploidy

frequency of aneuploidy increases as the mother ages As it’s believed to be in an increase in non disjunction during meiosis I with age in females

Klinefelter syndrome

• Extra X chromosome for males

• 1/500 - 1/1000 individual births

• Testes are reduced in size and are infertile

Turner syndrome

• loss of X chromosome in female

• 1/2500 individual births

• Lack of maturation of sex organs leading to being sterile (non child producing)

• Only known viable monosomy in humans

Cri du chat

• deletion of chromosome 5

• Cry sounds like mewing cat

• Intellectual disability

Wolf hirschhorn syndrome

• deletion in chromosome 4

• Intellectual disability

• Bone development issues

Effects of Nondisjunction in mitosis in embryogenesis

• if occurs early in embryogenesis it can cause loss of pregnancy and mosaicism

Effects of Nondisjunction in mitosis in CML

• chronic myelogenous leukemia is caused by an error in mitosis because of translocation in the pre white blood cell tissue which produces the philiadelphia chromosome