Today Genomic Imprinting and Epigenetics haploid X 23

Today: Genomic Imprinting and Epigenetics

haploid X 23 in humans diploid X 23 in humans Inheritance = The interaction between genes inherited from Mom and Dad.

Sex-linked traits: Genes on the X chromosome A= normal ; a= colorblind No one affected, female carriers similar to Fig 4. 13 50% of males affected, 0 % female affected 50% males affected, 50% females affected

Human sex chromosomes (includes Mic 2 gene) Fig 4. 14

Fig 3. 18 males and females may have different numbers of chromosomes

Tbl 7. 1 dosage compensation

Fig 7. 4 The epithelial cells derived from this embryonic cell will produce a patch of white fur While those from this will produce a patch of black fur At an early stage of embryonic development

Mammalian X-inactivation involves the interaction of 2 overlapping genes. Promotes compaction Prevents compaction

Barr body compaction is heritable within an individual

• A few genes on the inactivated X chromosome are expressed in the somatic cells of adult female mammals – Pseudoautosomal genes (Dosage compensation in this case is unnecessary because these genes are located both on the X and Y) – Up to a 25% of X genes in humans may escape full inactivation • The mechanism is not understood

Lamarck was right? Sort of… Epigenetics: http: //www. pbs. org/wgbh/nova/sciencenow/3411/02. html Image from: http: //www. sparknotes. com/biology/evolution/lamarck/section 2. rhtml

Genomic Imprinting • Genomic imprinting is a phenomenon in which expression of a gene depends on whether it is inherited from the male or the female parent • Imprinted genes follow a non-Mendelian pattern of inheritance – Depending on how the genes are “marked”, the offspring expresses either the maternallyinherited or the paternally-inherited allele **Not both

Genomic Imprinting: Methylation of genes during gamete production.

A hypothetical example of imprinting a B* A=curly hair A* b a=straight hair B=beady eyes b=normal *=methylation A* in males B* in females a B* A* b

A hypothetical example of imprinting a B* A=curly hair A* b a=straight hair B=beady eyes b=normal *=methylation A* in males B* in females A*a b. B* a B* A*a b. B* A* b

A hypothetical example of imprinting a B* A=curly hair A* b a=straight hair B=beady eyes A*a b. B* a B* A*a b. B* b=normal *=methylation A* in males B* in females A*a b. B Aa b. B* A* b

A hypothetical example of imprinting a B* A=curly hair A* b a=straight hair B=beady eyes A*a b. B* similar to Fig 7. 10 a B* A* b A*a b. B* b=normal *=methylation A*a b. B Aa b. B* A* in males B* in females A*b, A*B, ab, a. B Ab, AB*, ab, a. B*

Thus genomic imprinting is permanent in the somatic cells of an animal – However, the marking of alleles can be altered from generation to generation

Imprinting and DNA Methylation • Genomic imprinting must involve a marking process • At the molecular level, the imprinting is known to involve differentially methylated regions – They are methylated either in the oocyte or sperm • Not both

• For most genes, methylation results in inhibition of gene expression – However, this is not always the case

Changes in methylation during gamete development alter the imprint Haploid female gametes transmit an unmethylated gene Fig 7. 11 Haploid male gametes transmit a methylated gene

To date, imprinting has been identified in dozens of mammalian genes Tbl 7. 2

Tbl 7. 2

Imprinting plays a role in the inheritance of some human diseases: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) –PWS is characterized by: reduced motor function, obesity, mental deficiencies –AS is characterized by: hyperactivity, unusual seizures, repetitive muscle movements, mental deficiencies Usually, PWS and AS involve a small deletion in chromosome 15 –If it is inherited from the mother, it leads to AS –If it is inherited from the father, it leads to PWS

• AS results from the lack of expression of UBE 3 A (encodes a protein called EA-6 P that transfers small ubiquitin molecules to certain proteins to target their degradation) – The gene is paternally imprinted (silenced) • PWS results (most likely) from the lack of expression of SNRNP (encodes a small nuclear ribonucleoprotein that controls gene splicing necessary for the synthesis of critical proteins in the brain) – The gene is maternally imprinted (silenced)

The deletion is the same in males and females, but the expression is different depending on who you received the normal version from. Fig 7. 12