week 2 - single gene and sex linked inheritence (copy)

genes are

heritable factors located on chromosomes

two types of eukaryotic cell division

* somatic cell division
* division of normal cells
* nuclear division in somatic cells is mitosis
* sexual cell division:
* division of sex cells taking place in sex organs
* nuclear division in sex cells is meiosis

meiocyte

specialized diploid cell set aside to produce gametes by meiosis

* diploid cell in which meiosis takes place
* diploid meiocyte: 2n → n+n+n+n

diploid and haploids

n is the number of chromosomes in a genome, known as the **haploid number**

* mitosis:
* diploid mitosis: 2n→ 2n + 2n (genetically identical)
* 2 of each chromosome, one from each parent, for sexually reproducing organisms
* n pairs of chromosomes, chromosome pairs called homologous chromosomes or homologs
* haploid mitosis: n → n + n (genetically identical)
* one of each chromosome

how are daughter cells genetically identical to the parent cells in mitosis?

* each chromosome replicates to make two identical copies of itself, with underlying DNA replication
* cell makes a copy of each homolog
* when the cell divides, each daughter cell has the same chromosomal set as its progenitor

resulting gametes of diploid cell meiosis are

* haploid because although nuclear division occurs twice in meiosis, chromosome replication only occurs once
* 2n → n + n + n + n

DNA replication before mitosis

each chromosome is seen to have duplicated to form daughter chromatids which remain attached to each other at the centromere

* each chromatid represents one of two identical DNA molecules formed just before mitosis by DNA replication

mitosis is diploids

* each pair of chromatids aligns on the equatorial plane of the cell
* one sister chromatid is pulled into each daughter cell as the centromere divides
* Aa → Aa + Aa

meiosis in diploids

* also preceded by replication and chromosome condensation
* in the first division, centromere holding a pair of sister chromatids together does not divide
* one pair of chromatids is pulled into each daughter cell by spindles that attach to the undivided centromeres
* at the second division of meiosis, the centromeres divide; and now each chromatid is pulled into its own cell, which is now effectively haploid
* 1A:1a
* 4 haploids = **tetrad**

mitosis in haploids

* each somatic cell bears only one chromosome set
* for Aa:
* A → A + A
* or a → a + a

meiosis in haploids

* only occurs when two haploids unite to form a transient diploid meiocyte
* yeast example:
* meiocyte formed by the union of a haploid cell of a mutant, *r*, and a haploid cell of wild type *r+*
* transient diploid meiocyte is a heterozygote r+/r
* the four haploid cells produced are 1/2 r and 1/2 r+
* the four haploid nuclear products representing the meiotic tetrad remain together enclosed in a membranous sac
* called an **ascus** in yeast

structural differences between alleles at the molecular level

in wild type vs mutant alleles:

* generally found to be identical in most of their sequences and differ only at one or several nucleotides of the many nucleotides that make up the gene
* therefore, alleles are diff. versions of the same gene that arise via mutation
* \

mutations at gene sites

* protein-coding regions of a gene: exons
* mutations within exons change one or more amino acids and inactivate some essential part of the protein encoded by the gene
* important functional region of the gene is that encoding an enzyme’s active site; so this region is very sensitive to mutation
* minority of mutations are found to be in introns
* mutations within introns often prevent the normal processing of the primary RNA transcript

types of mutations

* null alleles - the proteins encoded by them completely lack function
* leaky mutations - reduce the level of enzyme function; some wild-type function seems to “leak” into the mutant phenotype
* silent mutations - functionally wild type, DNA sequencing often detects changes within a gene that have no functional impact at all

haplosufficiency

* one gene copy has enough function to produce a wild-type phenotype
* i.e. in a heterozygote that is +/*m*, the single functional copy encoded by the + allele provides enough protein product for normal cellular function
* assume a cell needs a minimum of 10 protein units to function normally
* each wild-type allele can produce 12 units
* +/+ will produce 24 units
* +/m will produce 12 units, in excess of the 10-unit minimum so mutant allele is recessive as it has no impact on heterozygote

haploinsufficiency

* null mutant allele will be dominant because, in a heterozygote (+/P), one wild-type allele cannot provide enough product for normal function
* i.e. cell needs a minimum of 20 units of this protein
* wild-type allele produces only 12 units
* +/+ makes 24 units, which is over the minimum
* +/P produces only 12; presence of the mutant allele in the heterozygote results in an inadequate supply of product and mutant phenotype ensues

segregation ratios: recessive mutant allele example

* mutant white flower plant (alb/alb) crossed with normal WT plant (+/+)
* F1: all alb/+
* F2:
* 1/4 is +/+
* 1/2 is alb/+
* 1/4 is alb/alb

segregation ratios: dominant mutant allele example

* wild type: long winged (+/+)
* mutant: short winged (SH/+ or SH/SH)
* mutant allele is dominant so it is represented by capital letters
* **P:** ^^+/+^^ **x** ^^SH/+^^
* F1a: 1/2 is +/+
* F1b: 1/2 is SH/+
* interbreed **F1a**: ^^+/+^^ **x** ^^+/+^^
* all progeny is +/+, as expected of a recessive WT allele
* interbreed **F1b**: ^^SH/+^^ **x** ^^SH/+^^
* 1/4 is SH/SH
* 1/2 is SH/+
* 1/4 is +/+

to test an individual with unknown heterozygosity via **testcross**

for an individual showing the dominant phenotype but of unknown genotype (A/?), cross them with recessive **tester** (a/a)

* A/? x a/a
* if progeny is 1:1 (half A/a and half a/a), individual was heterozygous (A/a)
* if all progeny shows dom. phenotype (A/a), individual was homozygous (A/A)
* unknown individual can also be selfed
* if heterozygous, progeny phenotype is 3:1
* if homozygous, all progeny is A/A

sexual dimorphism

individuals are either male or female, determined by **sex chromosomes**

autosomes and sex chromosomes in human body cells

46 chromosomes

* 22 homologous pairs of autosomes (A)
* 2 sex chromosomes
* females have a pair of identical sex chromosomes called the X chromosomes
* males have a nonidentical pair: one X and one Y
* Y chromosome is considerably shorter than the X
* females = 44A + XX - **homogametic**
* males = 44A + XY - **heterogametic**

dioecious species

plant species showing sexual dimorphism

* male and female sex organs on separate plants
* have X and Y determinism
* female plants bear flowers containing only ovaries
* male plants bear flowers containing only anthers

hermaphroditic (majority of plants)

* male and female organs are in the same flower
* i.e. mendel’s garden pea plant

monoecious

* separate male and female flowers on the same plant

homologous and differential regions of sex chromosomes

* differential regions contain most of the genes, have no counterparts on the other sex chromosome
* so differential regions in males are **hemizygous** (half zygous)
* X chromosome contains hundreds of genes
* most do not take part in sexual function but influence a great range of human properties
* Y chromosome contains only a few dozen genes
* some of which have counterparts on the X chromosome, but most do not
* those that do not take part in male sexual function
* pseudoautosomal regions 1 and 2
* short, homologous regions at each end of the sex chromosomes
* are autosomal-like
* regions pair during meiosis which is why in males, X and Y chromosomes can act as a pair and segregate into equal numbers of sperm

sex linkage

* inheritance pattern shown by genes in differential regions
* mutant alleles in differential region of X chromosome show **X linkage**
* mutant alleles in differential region of Y chromosome show **Y linkage**
* gene that is sex linked can show different phenotypic for each sex
* sex-linked inheritance patterns contrast with inheritance patterns of genes in autosomes, which are the same in each sex

x linked inheritance: first cross

in fruit flies: *w+* is the WT allele for red eyes and *w* is the mutant allele for white eyes, the alleles are of a gene located on the differential region of the X chromosome

* when white-eyed males crossed with red-eyed females
* all F1 progeny have red eyes
* males: w+ \~ ^^hemizygous WT^^
* females: w+/w \~ ^^heterozygous WT^^
* allele for white eyes is recessive
* crossing these red-eyed F1 males and females
* 3:1 F2 ratio of red-eyed to white-eyed flies, but all the white-eyed flies are males
* F1 females pass on *w* allele to half their sons who express it, and to half their daughters who do not express it because they must inherit the WT allele from their fathers

x linked inheritance: reciprocal cross

* cross between white-eyed females and red-eyed
* F1: all the females are red eyed, all the males are white eyed
* every female inherited the dominant w+ allele from father’s X chromosome
* every male inherited the recessive w allele from mother
* F2 consists of one-half red-eyed and one-half white-eyed flies of both sexes