Chromosomal Mutations Entire chromosomes extra/ missing(aneuploidy) Pieces of chromosome missing or moved onto a different chromosome. Identified by Karyotypes

Non-disjunction…….. how chromosomes go missing Non = not Dis = undo Junction= joining So non-disjunction is a failure to undo the joining of either: a) homologous chromosomes or b) sister chromatids

Non-disjunction of homologous chomosomes

Non-disjunction of sister chromatids

nondisjunction is the leading cause of pregnancy loss and birth defects. 90% of chromosome 21 nondisjunction are due to maternal meiotic errors homologous chromosomes are arrested in prophase I for 10 to 50 years.

Older moms have higher risk

Autosomal non-disjunction Too many or too few autosomes (C 1-22) Nearly always fatal (miscarriages) 3 Exceptions 1) Trisomy 18 – Edwards syndrome 2) Trisomy 13 - Patau syndrome 3) Trisomy 21 – Down syndrome

Trisomy 18 – Edwards syndrome 3 copies of chromosome 18 Half of infants with this condition do not survive beyond the first week of life. Small head (microcephaly) Some children have survived to the teenage years, but with serious medical and developmental problems.

Trisomy 13 – Patau syndrome More than 80% of children with trisomy 13 die in the first year. Small head (microcephaly)

Trisomy 21- Down Syndrome most common cause of human birth defects Down syndrome symptoms vary from person to person and can range from mild to severe Most are cognitively impaired Adults may live semi-independently

Sex Chromosome Non-disjuction At least one X chromosome is needed to live!! Females who are XXX are fine Males who are Xyy are fine y alone will not survive X alone gives Turner syndrome Xxy gives Kleinfelter’s syndrome

Turner Syndrome XO (monosomy) Girls with 1) short stature 2) poorly developed ovaries Treat with 1) growth hormones 2) female hormones like estrogen

Kleinfelter’s syndrome Men with 1) low testosterone levels 2) infertility Treated with hormone replacement therapy XXy

Why can we survive extra X or y? Dosage Compensation Theory : both ♀ & ♂ receive the same dose of X In ♀ one X Chromosome is inactivated Inactivated X condenses into a Barr body 75% of genes inactive

Mechanism of X inactivation In each embryonic cell the 2 X C pair up Then one of them activates its XIST gene XIST gene products (RNA) wrap up & inactivate that X C Which X is inactivated is random in each cell Occurs in morula stage of Embryo (ball of 2-16 cells)

Somatic tissues are a mosaic Patches of cells have different X C inactivated

Calico Cats & Sweat glands

How boys become boys 2 month old embryos = generic gonads SRY gene activation : make regulatory proteins Sex determining Region of the Y chromosome SRY regulatory proteins activate genes that cause baby to develop into a boy Absence of these …baby develops into girl

Altered Chromosome Structure 1) Deletion: lost section of C 2) Inversion: section of C flipped end for end 3) Translocation: section of C moved to new C 4) Duplication: section of C moves to sister C…one chromatid has 2 copies the other none