Lesson # 16Mutations

MutationsProduction of new alleles

Causes of mutations

Mutations appear due to a mistake during DNA replication or cell division. A new sequence of DNA is produced.

Mutagens: agent which produces or facilitates a mutation to occur.

Types of mutagens

Physical mutagen: radiation (X-rays or UV)

Chemical mutagens: some subtances can cause changes in genes. Like for examplepollutants, substances in tobacco. Risk of mutations increase with the increasedexposure.

Biological mutagens: some viruses can increase the frequency of genetic mutations

Some mutations result in the appearance of cancer cells Cells which avoidprogrammed apoptosis “death”.

Consequences of a mutation

Mutations do not always cause damage. Thanks to them, there is a greatergenetic variability amongst individuals in a population. Different alleles forthe same gene usually exist due to a mutation.

Blue eyes

Sometimes a mutation can result in an allele or version of a gene whichproduces a genetic disorder.

Colorblindness (Recessive sex-linked disorder)

Albinism (Recessive autosomal disorder)

Haemophilia (Recessive sex-linked chromosome)

Sickle Cell anemia (Incomplete dominance)

Achondroplasia (Dominant autosomal disorder)

Type of mutations

There are 3 main types of alterations in the genetic information of an

indivual due to a mutation.

Types of mutations

1. Gene mutations: new alleles are created for the same gene when there is a mistake

produced during the DNA replication during the S phase.

Gene mutations

Base substitution

Missense mutation: the change of the base causes a change in amino acid inserted in

the protein.

Nonesense mutation: the change of the base causes the protein to be terminated.

Silent mutation: the change of the base does not cause a change in amino acidsintroduced in the protein.

Insertion mutation :occurs when an extra nucleotide is added to the DNA strand

during replication. This can happen when the replicating strand "slips," or wrinkles,

which allows the extra nucleotide to be incorporated (Figure 2). Strand slippage

can also lead to deletion mutations.

Deletion mutation occurs when a wrinkle forms on the DNA template strand and subsequently causes a nucleotide to be omitted from the replicated strand (Figure

3).

Frameshift mutations

Ejercicio 1

A la vista de la siguiente tabla, indica cuales serán las diferencias entre

estas tres secuencias de ADN indicando la secuencia de aminoácidos en

cada caso:

a) UUAAAUGGGGCGUGGGAA;

b) UUAACCGGGGCGUGGGAA;

c) UUAACCGGAGCGUGGGAA.

Ejercicio 2

Al comparar la secuencia de aminoácidos de la hemoglobina procedente de un

enfermo de anemia falciforme con la de una persona sana, se observa que sólo se

diferencian en un aminoácido, el sexto de los 146 que forman la cadena. Si

observamos la cadena de nucleótidos para los 6 primeros aminoácidos vemos :

Secuencia de nucleótidos para la Hemoglobina Normal HbA

CTG ATC CCT GAG GAG AAG TCT

Secuencia de nucleótidos para la Hemoglobina causante de anemia falciforme HbS

CTG ATC CCT GTG GAG AAG TCT

1. Compara la secuencia de nucleótidos en el alelo normal y en el responsable de

la anemia falciforme. ¿En qué se diferencian?

2. ¿Qué tipo de mutación es la que causó esta diferencia? ¿En qué resulta esta

mutación a nivel peptídico?

3. ¿Qué ocurre con la función de una proteína cuando su secuencia de

aminoácidos sufre algún cambio?

Ejercicio 3

Dado el siguiente fragmento de ADN que será transcrito y traducido

5´ A A A T G C T A C A A T 3’

3´ T T T A C G A T G T T A 5´

1. Escriba la secuencia de nucleótidos y polaridad del ARN mensajero que se

sintetizaría utilizando como molde la cadena inferior del ADN

2. Proporcione los anticodones de los ARNt

3. Escriba la secuencia de aminoácidos del tetrapéptido que se sintetizaría

4. Explique qué ocurriría si en el triplete que codifica para Tyr se cambia la C

por A o G ¿Cuáles serían sus consecuencias?

Types of mutations

2. Chromosome structure mutations: when the structure of the chromosome is

not the correct one. This happens due to a mistake in the crossing over

which occurs in the formation of gametes (Prophase I of meiosis).

Types of mutations

3. Numerical mutations: An alteration in the number of chromosomes.

Trisomy 13 Patau syndrome

Trisomy 18 Edwards syndrome

Trisomy 21 Down syndrome

X0 Turner’s Syndrome

XXY Klinefelters síndrome

Normally due to a mistake in Anaphase I during meiosis (formation of a

gamet).