NAMA : DEWI FATMAWATI

NPM : 1814141016
PRODUKSI TERNAK

GEN TERANGKAI

A. Gen Terangkai (Linkage Gene)

Dua gen dikatakan saling terangkai apabila kedua gen tsb terletak didalam satu kromosom dan saling
berdekatan sehingga menyebabkan dlm proses pembelahan meiosis, kedua gen tesebut tidak sepenuhnya
terpisah secara bebas mengikuti hukum Mendel. Hal ini disebabkan karen kedua gen tersebut menunjukan
tendensi saling menempel satu sama lain.

1. Gen Terangkai pd Autosom

Percobaan yg mengarah pd penemuan adanya gen terangkai tlh dlkkn oleh Bateson dan Punnet pd
buncis sweet pea

2. Gen terangkai pd Sex Kromosom

Morgan melakukan percobaan pd lalat Drosophila melanogaster, untuk dua gen terangkai masing-
masing gen y (tubuh kuning) dan gen y+ (tubuh coklat) serta gen w (mata putih) dan w+ (mata
merah)

FINDING DESEASE GENES

This is an Irish family with an autosomal dominant disease mutation which causes blindness (the disease
is called RP). A large family like this is powerful (statistically) & can beused to find out which human
chromosome the disease gene is on.

 Genes are located on Chromosomes

They did not realise that chromosomes were involved in the mechanism of inheritance

• In the early 20th century, geneticists realised that chromosomes behaved just like the hypothetical “unit
factors” proposed by Mendel to explain inheritance

- they occur in pairs in diploid cells

- their number is halved during gamete formation
- fertilisation restores the diploid number
• They eventually proved that genetic information (genes) is located on the chromosomes
  Mendel's studies investigated the inheritance of 7 traits

• Each trait showed “independent assortment” i.e. the inheritance of one trait did not influence the
inheritance of the second trait

• Because of this, he observed the following ratios in the offspring

1. Monohybrid cross (inheritance of a single trait)

3 : 1 (dominant : recessive)
2. Dihybrid cross (inheritance of two traits)
9:3:3:1
Mendelʼs

 Is “independent assortment” always the case? No it depends on whether the genes are linked or
not

(a) Genes located on different chromosomes are not linked This allows independent assortment – in a di-
hybrid cross the traits show the classic 9:3:3:1 inheritance pattern
(b) Genes that are located very close together on the same chromosome may show complete linkage They
may be so close to each other that they cannot be separated by recombination during meiosis
(c) Genes located far apart on the same chromosome typically show incomplete (partial) linkage because
they are easily separated by recombination
Genetic maps or linkage maps Sturtevant proposed that recombination frequencies reflect the distances
between genes on a chromosome It is assumed that the chances of crossing over is equal at all points on a
chromosome If so, then the farther apart two genes are:

(a) the higher the probability that a cross-over will occur between them and therefore
(b) the higher the recombination frequency Why? Because the greater the distance between two genes
the more points there are between them where crossing over can occur

 Recombination frequencies can be used to construct a genetic map

• Recombination frequencies are approximately additive

• Recombination frequency between the body colour gene black
(b) and the eye colour gene cinnabar (cn) = 9%
• Recombination frequency between cinnabar and vestigial wing (vg) = 9.5%
• Recombination frequency between b and vg = 17%

GENETICLINKAGE
Discovery of Genetic Linkage

Genes on non-homologous chromosomes assort independently, but genes on the same chromosome
(syntenic genes) may instead be inherited together (linked), and belong to a linkage group.
 Classical genetics analyzes the frequency of allele recombination in progeny of genetic crosses
– New associations of parental alleles are recombinants, produced by genetic
recombination.
– Tests crosses determine which genes are linked, and a linkage map (genetic map) is
constructed for each chromosome.
MORGAN’s EXPERIMENTS

• Both the white eye gene (w) and a gene for miniature wings (m) are on the X chromosome.
• Morgan (1911) crossed a female white miniature (w m/w m) with a wild-type male (w+ m+/ Y).
– In the F1, all males were white-eyed with miniature wings (w m/Y), and all females were
wild-type for eye color and wing size (w+ m+/w m).
– In F2, the most frequent phenotypes for both sexes were the phenotypes of the parents in
the original cross (white eyes with miniature wings, and red eyes with normal wings).
MORGAN’S PROPOSAL

• During meiosis alleles of some genes assort together because they are near each other on the same
chromosome.
• Recombination occurs when genes are exchanged between X chromosomes of the F1 females
• Parental phenotypes occur most frequently, while recombinants less.
• Terminology
• Chiasma: site of crossover
• Crossing over: reciprocal exchange of homologous chromatid segments
• Crossing-over occurs at prophase I in meiosis; each event involves two of the four
chromatids. Any chromatids may be involved in crossing over.
Detecting Linkage through Testcrosses

Linked genes are used for mapping. They are found by looking for deviation from the frequencies
expected from independent assortment.
A testcross (one parent is homozygous recessive) works well for analyzing linkage

Chi-square for analysis of linkage

• A null hypothesis (‘the genes independently assort’) is used because it is not possible to predict
the phenotype frequencies produced by linked genes.
Concept of Genetic Map

In an individual heterozygous at two loci, there are two arrangements of alleles:

– Cis (coupling) arrangement: has both wild type alleles on one homologous chromosome,
and both mutants on the other (e.g., w+ m+ and w m).
– Trans (repulsion) arrangement: has one mutant and one wild-type on each chromosome
(e.g., w+ m and w m+)
– A crossover between homologs in cis arrangement results in a homologous pair with the
trans arrangement. A crossover between homologs in the trans arrangement results in cis
homologs.
Drosophila Crosses

They showed that cross over frequency for linked genes (measured by recombinants) is characteristics for
each gene pair. The frequency stays the same, whether the genes are in coupling or in repulsion.
First Genetic Map

• Three X-linked genes

• Crosses gave the following recombination frequencies
Gene Mapping Using Two-Point Testcrosses

With autosomal recessive alleles, when a double heterozygote is testcrossed, four phenotypic classes are
expected.
• For autosomal dominants
• For X-linked recessives
• For X-linked dominants
• Phenotypes obtained in these crosses
GENETIC MAP

Genetic map is generated from estimating the crossover rate in a particular segment of a the chromosome.
It may not exactly match the physical map because crossover is not equally probable at all sites on the
chromosome.
LINKED or NON-LINKED

• A recombination frequency of 50% means that genes are unlinked. There are two ways in which
genes maybe unlinked:
– They may be on separate chromosomes.
– They may be far apart on the same chromosome.
MULTIPLE CROSSOVERS
If the genes are on the same chromosome, multiple crossovers can occur. The further apart two loci are,
the more likely they are to have crossover events take place between them. The chromatid pairing is not
always the same in crossover, so that 2,3, or 4 chromatids may participate in multiple crossover.
Mapping using three-point testcrosses
• Geneticists design experiments to gather data on several traits in 1 testcross. An example of a
three-point testcross would be
– p+r+j+/p r j X p r j / p r j
– In the progeny, each gene has two possible phenotypes. For three genes there are
(2)^3=8 expected phenotypic classes in the progeny.
Establishing the order of genes

• The order of genes on the chromosome can be deduced from results of the cross. Of the eight
expected progeny phenotypes:
– Two classes are parental (p+ r+ j+/ p r j and p r j / p r j) and will be the most abundant.
– Of the six remaining phenotypic classes, two will be present at the lowest frequency,
resulting from apparent double crossover (p+ r+ j / p r j and p r j+ / p r j). This
establishes the gene order as p j r.
Calculating the recombination frequencies

• Cross data is organized to reflect the gene order, and this example the region between genes p and
j is called region I, and that between j and r is region II.
• Recombination frequencies are now calculated for two genes at a time. It includes single
crossovers in the region under study, and double crossovers, since they occur in both regions.
• Recombination frequencies are used to position genes on the genetic map (each 1%
recombination frequency = 1 map unit) for the chromosomal region.
• Recombination frequencies are not identical to crossover frequencies, and typically underestimate
the true map distance
Interference and Coincidence

• Characteristically, double crossovers do not occur as often as expected from the observed rate of
single crossovers. Crossover appears to reduce formation of other chiasmata nearby, producing
interference.
– Interference = 1 is total interference, with no other crossover occuring in the region.
Coefficient of coincidence express the extent of interference

• Interference = 1-coefficient of coincidence. The values are inversely related.

 • A value of 1 means the number of double crossovers that occurs is what would be predicted on
the basis of two independent events, and there is no interference.
• A value of 0 means that none of the expected crossovers occurred, and interference is total.
Calculating accurate map distances

• Recombination frequency generally underestimates the true map distance:

– Double crossovers between two loci will restore the parental genotype, as will any even
number of crossovers. These will not be counted as recombinants, even though
crossovers take place.
– A single crossover will produce recombinant chromosomes, as will any odd number of
crossovers. Progeny analysis assumes that every recombinant was produced by a single
crossover.
– Map distances for genes that are less than 7 mu apart are very accurate. As distance
increases, accuracy declines because more crosses go uncounted.
Mapping functions

• Mathematical formulas used to define the relationship between map distance and recombination
frequency. They are based on assumptions about the frequency of crossovers compared with
distance between genes.
Genetic markers

• The number of physically observable genes in humans is very small. Consequently, human
genetic maps based on these were not useful.
• The development of genetic loci that could be observed at the level of DNA was essential to
modern human genetics.
• Two alleles (ie, D vs d) needed to be detected, at the DNA level, to define a DNA “marker”
locus.
• There are several technical solutions to the observation of DNA differences.
• In a DNA marker, somewhere in the 100-1000 bp amplified region there must be a DNA
sequence difference (polymorphism) between individuals.
• The most common DNA marker systems examine the number of repeated units in a simple
sequence repeat motif, such as CACACACACACACAC.
• Individuals can vary considerably in the number of CA blocks, making these types of DNA
sequences very useful population markers.
• Single basepair differences, however, are much more common in the genome and so have great
potential.
 • Single basepair differences are often called SNPs (Single Nucleotide Polymorphisms).
• However, the frequency of individuals being different at a single base is much less than
CACACACA repeat motifs.
• Genetic markers are simply “signposts” along the chromosomes that are readily detected and
comparable between laboratory experiments.
• Ideally, genetic markers should be readily available at a high density across the genome
(>100,000).
• The markers should be easily communicated between lab groups and easily quality controlled.
• And, the work to obtain the marker information should be low error and inexpensive

Mitotic recombination

• Crossing over during mitosis was first observed by Stern (1936) in Drosophila.
– The alleles involved are sex-linked and recessive to the wild type:
• Y produces yellow body color instead of wild type grey.
• Sn produces short, twisty bristles (“signed”) rather than the wild-type long,
curved ones. Bristles follow body color (y+/- are black, and y/y are yellow.
• Female progeny from the cross
• y+ sn / y+ sn x y sn+ /Y
• Generally have wild type phenotype of grey bodies and normal bristles, corresponding to their
genetoype (y+ sn / y sn+). But exceptions:
– Some flies had patches of yellow and/or signed bristles. This could be explained by
nondisjunction or chromosomal loss.
– Other flies had twin spots, adjacent regions of bristles, one yellow and the other signed, a
mosaic phenotype. The spots are reciprocal products of the same genetic event, a mitotic
crossing over.
– Mitotic crossover occurred either between the centromere and the sn locus or between the
sn and the y locus.
Mechanism of Mitotic Crossing over

• A rare event occurring only in diploid cells, mitotic crossover can result when replicated
chromatids come together to form a structure similar to the four-strand stage in meiosis.
• If the starting genotype is d+ e / d e+, the two possible orientations of the resulting chromatids
are:
 – One cell with d+ e+ / d+ e+, and one with the d e/ d e. These are the ones that are useful
for mapping, because the recessive phenotype can be observed in progeny of the d e / d e
cells.
– Reversal of the alleles, d e+ / d+ e. Phenotypically indistinguishable from non-
recombinant cells, there are not useful for mapping, but are nonetheless derived from a
crossover event.

Retinoblastoma

• Most common childhood eye cancer.

– Non hereditary (sporadic) form occurs in an individual with no family history of the
disease, and affects only one eye (unilateral).
– Heteditary form affects both eyes (bilateral) and usually occurs at an earlier age than
sporadic.
– A single gene (Rb) on chromosome 13q14 involved.
• In hereditary retinoblastoma, tumor cells have mutations in both copies of this
gene, while other cells in the same individual are heterozygous. The disease is
caused by a second mutation that affects the normal RB allele.
• The second mutation is often identical to the one on the other chromosome,
strong circumstantial evidence that the wild-type copy of the gene is somehow
replaced by the inherited mutated allele. One possible explanation is mitotic
recombination.