Unformatted text preview: BICD 130 Embryos, Genes, and Development Review Session for Final Exam Sunday March 19 1-3 PM PCYNH 109 In vitro fertilization (IVF) as a therapy for infertility Methods for improving the success rate of IVF Assisted hatching Intracytoplasmic sperm injection Only a minority of human fertilization events result in term pregnancies Abnormalities in human development Abnormalities caused by genetic events are called malformations Abnormalities caused by exogenous agents are called disruptions Down syndrome results from trisomy for chromosome 21 Blue: Chromosome 13 Pink: Chromosome 21 Down syndrome is the most frequent genetic disorder in humans Genes Included in the Down Syndrome Critical Region (DSCR) DSCR1: overexpressed in Down syndrome; encodes a protein that inhibits calcineurin (major calcium regulatory protein) DSCAM: alternatively spliced transcript encodes a cell adhesion protein involved in axon guidance A recent challenge to the DSCR model Science 306: 687-690 (2004) These investigators used chromosome engineering to create mice that were trisomic or monosomic for only the mouse chromosome segment orthologous to the DSCR. They found that DSCR genes are not sufficient and are largely not necessary to produce the characteristic craniofacial phenotype of DS Fragile X syndrome results from expansion and hypermethylation of CGG repeats in the FMR1 gene FMR1 encodes an RNA-binding protein involved in targeting and translation of mRNAs with roles in synapse formation Mutations in genes encoding transcription factors are responsible for many human genetic diseases Positional cloning of PAX6, the gene associated with aniridia in humans A candidate gene approach to identifying the locus associated with Waardenburg syndrome type 2 Mutations in developmental pathway genes often have pleiotropic effects (multiple defects) Two types of pleiotropy Abnormalities in human development Abnormalities caused by genetic events are called malformations Abnormalities caused by exogenous agents are called disruptions Teratogens
Exogenous agents that cause disruptions of normal development, resulting in congenital anomalies Different organs show different times and degrees of sensitivity to teratogens Known and likely teratogenic agents in humans Ethanol is a powerful human teratogen Fetal alcohol syndrome (FAS) Normal Exposure to diethylstilbestrol (DES) in utero Causes morphological abnormalities of the reproductive tract (females) Leads to abnormal genitalia (males)
DES was once (1940 s to 1960 s) prescribed to pregnant women to prevent miscarriage and premature labor DES Genes of the Hoxa cluster in the mouse are expressed in nested fashion in the Mllerian duct Exposure to DES represses Hoxa-10 expression in the Mllerian duct DES acts through the estrogen receptor to block Wnt7a expression Stem cells Can divide indefinitely Division generates a more specialized cell and another stem cell Generalized stem cell lineage Types of stem cells Embryonic: pluripotent Adult: restricted potency (e.g., hematopoietic, epithelial, intestinal, neural); essential for tissue homeostasis A stem cell lineage that gives rise to lymphocytes and blood cells Methods for obtaining human pluripotent stem cells Methods for obtaining human pluripotent stem cells ' Potential therapeutic use of embryonic stem (ES) cells Differentiation of mouse ES cells into lineagerestricted stem cells is controlled by growth medium Vectors for introducing exogenous genes for gene therapy Vectors for introducing exogenous genes for gene therapy Gene therapy following therapeutic cloning in the mouse ...
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