Week 3 Study PDF

MOLBIOL/BIOL 2C03 – Genetics Week 3 Faizan Saleem 1  Sex determination: there are many ways to do this! Sex determination can be environmental (ESD) or genetic (GSD) Definitions: Genetic/chromosomal sex (based on what chromosomes an i...

MOLBIOL/BIOL 2C03 – Genetics Week 3 Faizan Saleem 1  Sex determination: there are many ways to do this! Sex determination can be environmental (ESD) or genetic (GSD) Definitions: Genetic/chromosomal sex (based on what chromosomes an individual has; multiple types) Phenotypic sex (based external appearance; many species have two sexes, some have one, some have more than two) 2  Sex Determination in Drosophila Males are the heterogametic (XY) sex. Females are homogametic The X/A ratio (X/autosome ratio) determines gender Females: X/A ratio of 1.0 (2 X and 2 A) Males: X/A ratio of 0.5 (1 X and 2A) Females have two X chromosomes and males have one X chromosome Female flies: XX (normal) or XXY Male flies: XY (normal), XYY, or XO XXX and YO flies are never seen in nature 3 Sex Determination in placental and marsupial mammals Determined by the presence or absence of the Y-linked femalea dre gene Sry Females: ifsor havesa Usually: XX asababs make Rarely: XO, XXX, XXXX Males: Usually: XY Rarely: XXY, XYY, XYYY 4  In humans and many other sexual species, sexual differentiation results in a continuum of phenotypes that includes intermediates Sometimes the genetic sex does not match the typical phenotypic sex 5 Other examples of mutations that affect sexual differentiation of humans SRY expression Congenital adrenal hyperplasia(CAH): in males mutations in the CYP21 gene prevent degradation of testosterone and derivatives Boys with CAH: very early pubescence Girls with CAH: enlarged clitoris, masculinized body hair 6 Other examples of mutations that affect sexual differentiation of humans hormones Androgen insensitivity syndrome: genetically male (XY) individuals have a defective androgen receptor; external appearance is female, but gonads are undifferentiated; individuals are sterile 7 ZW Sex Determination (female heterogamy) ZW system: birds, butterflies, moths, some reptiles, fish, and amphibians Females: ZW Males: ZZ 8  ZW Sex Determination (female heterogamy) Reciprocal crosses illustrate female heterogamy in chicken Females (instead of males) are hemizygous and express the trait of a recessive Z-linked allele (white feathers) F2 crosses also are consistent with Z-linkage 9  A General Review before Further begin & Analysis of X-Linked Traits The father passes his X sex chromosome (and all its genes) to his daughters and his Y sex chromosome (with its genes) to his sons. Genes act in pairs, one from each parent for the females. For this mode of inheritance, males get their gene for the trait from their mother. Gene pairs separate during meiosis and the formation of the sex cells along with the chromosomes. When the sperm fertilizes the egg, the father’s genes (and chromosomes) join the mother’s, or both contribute to the genetic makeup of the offspring. One form of a gene may be dominant over another form which is recessive and the dominant form would be expressed. 10  X-Linked recessive inheritance of red– green color blindness In this pedigree, mostly males have this condition (there is one exception) The “recessive” or “dominance” of the allele refers to its effect in females 11  Patterns for X-linked Recessive Inheritance The trait is more common in males than in females. If a mother has the trait, all of her sons should also have it. There is no male-to-male transmission. It has the same inheritance patterns as autosomal recessive for human females. The son of a female carrier has a 50 percent chance of having the trait. Mothers of males who have the trait are either heterozygous carriers or homozygous and express the trait. 12 X-Linked recessive inheritance of red– green color blindness eates muvemu Question: What are the possible genotypes and phenotypes of parents of a color-blind woman? 13 Hemophilia A is also an X-Linked recessive trait British Royal Family 14  X-Linked Dominant Trait Transmission Congenital hypertrichosis (CGH): Excessive body hair affecting both males and females All carriers of the mutant allele also express the trait A difference from an autosomal dominant mutation is that a father cannot pass the trait to his son 15 15  Patterns for X-linked Dominant Inheritance All daughters of a male who has the trait will also have the trait. There is no male-to-male transmission; the trait follows the inheritance of the X-chromosome. Sons can have the trait only if their mother also has the trait. Same inheritance pattern as autosomal dominant traits in human females. 16  Y-Linked Inheritance Y-linked traits: exclusively male-to-male transmission Mammals have ~80 genes on the Y chromosome Genes on the human Y chromosome do not have homolog on the X chromosome Hypertrichosis of the ears, webbed toes, and porcupine man 17  The problem with sex chromosomes… Males and females have the same number of autosomal chromosomes but females have twice as many X chromosomes as males This creates an imbalance in the “dosages” of X-linked genes This means that females could have twice as much protein in the cell from X-linked genes compared to males Biology is very sensitive to this kind of dosage difference (e.g. trisomy in humans) 18 Dosage compensation evolved multiple times to equalize expression of X-linked genes In placental mammals, one X in females is silenced (X inactivation) more In fruit flies, the X in males is upregulated In nematodes, both X- less linked alleles in females have lower expression 19 Lucchesi et al. 2005 Dosage compensation evolved multiple times to equalize expression of X-linked genes All of these mechanisms cause the dosage of X- linked genes to be similar in males and female But it does not have to be the same as the autosomes (e.g., it is not the same in humans or nematodes) 20 Lucchesi et al. 2005 X-inactivation: Interphase nucleus: female cell we Yellow: fluorescent probe that recognizes the X- chromosome Murray Barr and Ewart Bertram, 1949. Condensed mass in nucleus of female cells in cats, not male. Susumu Ohno, 1960. Proposed that the mass was the X-chromosome  How does X inactivation happen in (female) placental mammals? M: maternal X chromosome P: paternal X chromosome 22 22 What happens if there are genes on the X-chromosome? Genetics - calico cats Orange gene is on the X- chromosome. O = orange o = black O/o female cat Male offspring are 50 % O/Y orange 50% o/Y black  Orange versus black: determined by the gene, O. This cat is heterozygous, genotype: Oo Phenotype: Some cells are O = orange Some cells are o = black White determined by another gene on an indicates an allele that is present, but is autosome. White is not contributing to the phenotype. dominant.  Coat Color in (female) cats is visibly mosaic due to X inactivation Mosaicism may also be visible in women with X- linked skin conditions. “Lines of Blaschko” are due to different patches of skin that are descended from embryonic cells with different X chromosomes being inactivated 25  Practice Problem (sex-linked Trait) & if dominant one of the parents wouldexpresrait 1. Is it recessive or dominant? recessive 2. Is it x-linked? If yes, then why? her 3. What is the genotype of individual III-2? heterozygous bic is affected Son 26  Homework Assign genotypes to each individual of the pedigree. 27